Estrogens during pregnancy. Estrogen during pregnancy: the norm, violation and what affects the effect of estrogen on the course of pregnancy

UDC 577.175.64: 618.2 (047.31) DOI:

CURRENT CONCEPTS OF THE ROLE OF ESTROGENS DURING PREGNANCY

(LITERATURE REVIEW)

I. V. Dovzhikova, M. T. Lutsenko

Federal State Budgetary Scientific Institution "Far Eastern Scientific Center of Physiology and Pathology of Respiration", 675000, Blagoveshchensk, st. Kalinina, 22

The purpose of the article is to analyze the importance of estrogen during pregnancy. The mechanism of hormone effects is briefly outlined. The influence of estrogens on the uteroplacental blood flow, their necessity for starting the program of tissue morphogenesis in the placenta and uterus, the effect on the production of other steroid and protein hormones, the stimulating effect on the work of 11p-hydroxy-steroid dehydrogenase, and the regulation of the expression of low-density lipoproteins are considered. Shown are growth factors serving as mediators of estrogen. The conclusion is presented that at the beginning of pregnancy, estrogens promote morphological and functional growth, development and differentiation of the placenta; in the second half of pregnancy, estrogens stimulated functional maturation. In addition, hormones play an important role in the development of the lungs, kidneys, liver, ovarian follicles, fetal bone tissue and contribute to the formation of various changes in the mother's body necessary for maintaining pregnancy.

Key words: estrogens, mechanism of action, pregnancy.

MODERN CONCEPTS OF ESTROGENS ROLE AT PREGNANCY (REVIEW)

I.V. Dovzhikova, M.T. Lutsenko

Far Eastern Scientific Center of Physiology and

Pathology of Respiration, 22 Kalinina Str., Blagoveshchensk, 675000, Russian Federation

The article analyzes the importance of estrogen during pregnancy. The mechanism of hormones effects is summarized. The effect of estrogen on utero-placental blood flow, its necessity to run tissue morphogenesis in placenta and uterus, the impact on other steroid and protein hormones production, stimulating effect on 1ip-hydroxysteroid dehydrogenase work, regulation of LDL expression are studied. The growth factors that are mediators of estrogen are shown. There was made a conclusion that in early pregnancy estrogens contribute to morphological and functional growth, development and differentiation of placenta and in the second half of pregnancy estrogens stimulate functional maturation. Furthermore, hormones play an important role in the development of lung, kidney, liver, ovarian follicles, fetal bone and promote the formation of different changes in the mother necessary for the maintenance of pregnancy.

Key words: estrogens, mechanism of action, pregnancy.

Female sex steroid hormones play a huge role during gestation. Recently, however, research efforts have focused mainly on progesterone and its metabolites. In the study of estrogens, the emphasis is on the analysis of their effect outside of pregnancy (the mechanism of carcinogenesis, the state of bone tissue, cardiovascular and nervous systems). Reviews on the value of estro-

genes during pregnancy are not represented enough in the modern literature available to us. The aim of our work was to analyze the action of these hormones during the hereditary period.

The mechanism of action of estrogens

Estrogens, like other steroid hormones, act through estrogen receptors (ERs) - members of the steroid-receptor superfamily - which are simultaneously transcription factors. The most well-studied receptors of the most active estrogen - estradiol - a and p. REa are localized in the organs of the female reproductive system, as well as in the placenta - syncytiotrophoblast and cytotrophoblast. RERs are found in the testes, ovaries, spleen, thymus, adrenal glands, pituitary gland, brain, kidneys, and skin. Studies have shown that these two subtypes of EC react differently depending on the ligand and may have different roles in gene regulation. The existence of one more ER, the so-called receptor, which penetrates the membrane 7 times and is associated with the G-protein (GPER), has been proven. In addition to the receptor mechanism of action, estrogens have so-called “fast” non-genomic effects. Such effects, occurring over a short period of time, have been described for other steroid hormones (eg, progesterone). In the placenta, the actions of estrogens are carried out in the classical way - through receptors.

It is believed that the importance of estrogen during gestation is insignificant. This point of view is based on studies of the role of hormones in conditions of their suppressed synthesis (for example, with congenital lipoid hyperplasia of the adrenal glands, insufficiency of placental aromatase or sulfatase). In such studies, it was found that a decrease in estrogenesis did not lead to abortion. The question arises: why does the placenta produce such a large amount of estrogen? To answer it, let's try to understand the role of these hormones during pregnancy.

Effect of estrogens on uteroplacental blood flow

One of the most important functions of estrogens is their ability to influence the uteroplacental blood flow. Moreover, the most effective hormone in this case is estriol, the amount of which increases sharply during gestation.

The mechanisms of this influence are different. Estrogens affect the vascular endothelium by increasing the production of a number of vasodilators, such as nitric oxide, endothelial hyperpolarization factor, and prostacyclin. The activation of endothelial NO synthase by estrogens can occur by three different mechanisms: through stimulation of the expression of the enzyme gene by means of REa; through the activation of a signaling pathway consisting of phosphoinositide-3-kinase - protein kinase

ACT, which phosphorylates NO synthase, which leads to an increase in the activity of the latter; and through increased expression of calmodulin, which is required for calcium-dependent stimulation of NO synthase. Estrogens shift the balance of prostanoid synthesis to the vasodilator, prostacyclin (PGI2). They increase PGI2 production through stimulation of cyclooxygenase 1 and PGK synthase activity. At the same time, estrogens inhibit the induction of type 2 cyclooxygenase and, accordingly, the synthesis of prostaglandin E2 in the vessels.

In addition, estrogens interfere with the action of traditional vasoconstrictors (for example, endothelin 1) and reduce the expression of angiotensin-converting enzyme in endothelial cells, as well as angiotensin II receptor 1. It has also been found that estrogens affect the blood coagulation system: they lower the level of fibrinogen, antithrombin III and protein S.

With the advent of powerful new molecular research methods, it is becoming clear that the mechanisms of action of estrogens are much more varied and complex than originally thought.

Estrogens and morphogenesis of uterine and placental tissues

Estrogens are necessary for starting the tissue morphology program in the placenta and uterus. It was previously found that, despite the fact that in vivo cells of the uterus were highly sensitive to estrogens, in vitro they almost completely ceased to respond to physiological doses of these hormones. This fact was explained by the presence of growth factors in the body, which serve as mediators of steroid hormones due to autocrine and paracrine action, which contributes to the regulation of proliferation and differentiation processes. Estrogens potentiate the effects of a number of factors required for morphological and functional differentiation.

For maximum exchange between the circulatory systems of the mother and the fetus, it is necessary that the capillaries account for more than half the mass of the placental villi. Growth factors and adhesion molecules required for angiogenesis include: fibroblast growth factor, vascular endothelial growth factor, insulin-like growth factor, epidermal growth factor family, angiopoietins, nitric oxide, and various integrins required for cell attachment.

One of the most potent and widely recognized factors affecting vascular development in the villi is VEGF, a vascular epidermal growth factor, also known as vascular permeability factor or vasculotropin. VEGF plays a key role in stimulating the assembly of endothelial cells into capillaries. During pregnancy, the activation of this protein by estrogens underlies vasculogenesis (the formation of the embryonic vascular system) and angiogenesis (the growth of new vessels in the already

existing vascular system). It stimulates mitosis, activates the action of serial proteases (iRA and tPA) and collagenases, increases the chemotaxis of endothelial cells, induces the permeability of endothelial cells, leading to the extravasation of plasma proteins to provide a matrix for the migration of endothelial cells. Most of the VEGF is produced in the cytotrophoblast (in comparison with syncytiotrophoblast and Kashchenko-Gofbauer cells).

When stimulating vascular morphogenesis, VEGF acts in conjunction with two proteins - angiopoietin-1 and angiopoietin-2. It has been established that type I angiopoietin is released from both cyto- and syncytiotrophoblast, while the expression of type II angiopoietin is found mainly in cytotrophoblast. Angiopoietin-1 promotes the association of endothelial cells, smooth muscle cells, and pericytes for the maturation of nascent blood vessels. Angipoietin-2, on the other hand, loosens the vascular wall so that endothelial cells become available to VEGF. Together, it provides vasculogenesis and thus blood flow in the placenta and hence the growth and development of the fetus.

Estrogens regulate the expression of vascular growth factor and angiopoietins through their receptors, paracrine promoting the advancement of the vascular system of the placental villi in the first half of pregnancy. The exact mechanism of regulation is not known exactly, there are suggestions about the involvement of various transcription factors (for example, the protein hypoxia-inducible factor - H1T-1).

The main factor of growth of fibroblasts is well studied - oFGF, which is also regulated by estrogens. oFGF, inducing the proliferation of endothelial cells, leads to an increase in the number of vessels. It also controls the production of enzymes that cause remodeling of the extracellular matrix, in particular collagenase, matrix metalloproteinases and a plasmin gene activator that promote vasodilation, and is responsible for chemotaxis. In addition, it was revealed that changes in the ligand / oFGF receptor system can cause bleeding by disrupting the expression of integrins, which are cell adhesion molecules and are closely involved in the processes of angiogenesis.

Estrogens have a potentiating effect on the epidermal growth factor (EGF) family. It is believed that EGF facilitates implantation by promoting blastocyst growth and trophoblast proliferation. Estrogens potentiate the action of TGF-R, which belongs to the EGF family. The transforming growth factor regulates cell growth, is involved in the processes of apoptosis and tissue remodeling, and plays a fundamental role in the formation of the extracellular matrix.

The most important effect of EGF is its involvement in the regulation of the expression of the insulin-like growth factor, IPFR-1. According to many studies

niyam, IPFR-I and, probably, IPFR-II are mediators of estrogen action in tissues. Estrogen stimulates the production and expression of IPGF-I and inhibits the binding protein insulin-like growth factor (IPGFR-3). IPFRSP monitor the activity of IPFR in the bloodstream and tissues. IPFR ensures cell proliferation, differentiation and survival. IPFR receptors have tyrosine kinase activity and use adapters - IRS-I / Shc as secondary messengers in signal transmission into the cell, which, through the intracellular signaling pathway IRS / PI3K / AKT, in turn, ensure cell survival through Shc / Ras / Crb2 / MAP kinases - cell proliferation. Many authors insist on the leading role of this factor in myocyte proliferation.

Thus, estrogens play a key role in the process of cell proliferation. In this case, hormones act not only through growth factors. Cell proliferation is regulated by the mechanisms of control of the cell cycle, which includes a set of cyclin-dependent kinases (CDK-cyclin-dependent kinases, serine / threonine-protein kinases) together with their activators (cyclins) and inhibitors. Estradiol directly (through a signaling pathway that includes the sequence phosphoinositide-3-kinase - AKT - GSK-3P) regulates the cell cycle. In addition, estradiol accelerates the progression of the cell cycle from G to S phase by increasing the activity of CDK4 and CDK2, stimulating the expression of cyclin D1, and reducing the level of CDK inhibitors.

Estrogens and mitochondria

Estrogens are capable of profoundly affecting mitochondrial functions by increasing the activity of oxidative phosphorylation and, at the same time, they reduce the production of superoxide in mitochondria, which is accompanied by a decrease in the level of lipid peroxidation. The exact mechanism of action of estrogens is unknown. A direct genomic effect is not excluded, since estrogen receptors are found on mitochondria. In addition, estradiol affects mitochondrial function by modulating the activity of proteins of the 1 PPARg coactivator family (gamma peroxisome proliferator receptors), which are regulators of mitochondrial protein expression.

The role of estrogens in the second half of pregnancy

So, at the beginning of pregnancy, estrogens contribute to the morphological and functional growth, development and differentiation of the human placenta. In the second half of pregnancy, estrogens stimulated functional maturation, which manifested itself in several ways. First, in the form of regulation of the expression of LDL receptors, which specifically stimulates the absorption of lipoproteins. It should be noted that this fact took place only in the placenta and did not affect the maternal organism. Secondly

rykh, estrogens activate the enzyme cytochrome P450scc, thereby promoting the biosynthesis of progesterone in the placenta. In other words, some steroid hormones influence the formation of others and thus regulate their action.

Estrogens, in particular estradiol, stimulate the production of chorionic gonadotropin. The hormone has a trophic effect on the implanted egg and adjacent tissues, stimulates the development and secretory activity of the corpus luteum, participates in the regulation of the biosynthesis of progesterone and estrogens in the placenta, promotes the mutual conversion of estrogens and androgens. The data on another protein hormone, chorionic somato-mammotropin, are contradictory. Some researchers believe that estrogens stimulate hormone production in the placenta, while others, on the contrary, suppress it. Chorionic somatomammotropin, also known as placental lactogen, is a special peptide hormone produced only by the placenta, it plays an important role in the maturation and development of mammary glands during pregnancy and in their preparation for lactation.

At the same time, estrogens regulate the localization and development of the 11p-hydroxysteroid dehydrogenase enzyme system in the syncytiotrophoblast, which increases the transplacental oxidation of maternal cortisol to cortisone and leads to the maturation of the hypothalamus-pituitary-adrenal axis in the fetus at the end of pregnancy. Before its formation, cortisol from the mother freely penetrated the fetus and inhibited fetal glucocorticoid synthesis. After the formation of the enzyme system, 11p-hydroxysteroid dehydrogenase II inhibits 90% of corticosteroids entering the placenta. As a result of this cascade of events, there is an increase in the pituitary expression of proopiomelanocortin / ACTH and key enzymes, for example, 3p-hydroxysteroid dehydrogenase and P450c17. This leads to adrenocortical self-sufficiency: the adrenal cortex begins to produce glucocorticoids, which are necessary for fetal maturation and neonatal survival.

Estrogen modulates steroidogenesis in the fetal adrenal glands in several ways. Estradiol indirectly increases the production of dehydroepiandrosterone in the fetal adrenal glands by increasing the production of ACTH, which stimulates the synthesis of this estrogen precursor. At the same time, it directly inhibits the production of dehydroepiandrosterone through a decrease in the activity of the P450c17 enzyme. The latter also helps to maintain normal estrogen levels during pregnancy.

Estrogens control the development of fetal ovarian follicles. The regulation of folliculogenesis by estrogens is proved by the presence of ER and a number of experiments in which the number of follicles significantly decreased when the synthesis of these hormones was suppressed. Oocytes need nutrients that

are obtained from the cells surrounding them. Microvilli are of great importance in this process. Estrogens regulate the formation of microvilli in the ovaries of the fetus. In the absence of hormones, oocytes had a significantly smaller number of villi on the plasma membrane, which ensure the absorption of the nutrient substrate from the surrounding cells. As for the mechanism by which estrogens regulate, it remains to be investigated. It is assumed that the development of oocyte microvilli requires phosphorylation of the binding protein β-ezrin and expression of α-actinin, which is necessary for the final stage of microvilli formation. The expression of a-actinin, as well as the localization of ezrin phosphate and the SLC9A3R1 gene (encoding an ezrin binding protein) in the oocyte membrane are regulated by estrogens.

In addition, estrogens play an important role in the development of the lungs, kidneys, liver, and fetal bone tissue.

Effects of estrogen on a woman's body during pregnancy

Estrogens affect not only the development of the fetus and placenta, but also contribute to various changes in the mother's body necessary to maintain pregnancy.

Under the influence of estrogens, not only blood circulation in the uteroplacental region changes, but also in the entire cardiovascular system, including the cerebral blood flow of a pregnant woman. For example, during pregnancy, there is a 40-50% increase in plasma volume, a 25% increase in the mass of red blood cells and, consequently, an increase in the blood volume of the mother as a whole. These changes are associated with an increase in cardiac output, an increase in uteroplacental blood flow, which accounts for as much as 25% of the total volume of cardiac output, and a 20-35% decrease in total peripheral resistance. The exact mechanisms of hormone action are still being studied. For example, plasma volume increases as a result of estrogen stimulation of the renin-angiotensin system, which leads to an increase in aldosterone production and, consequently, reabsorption of sodium and water ions.

Estrogens increase the availability of protein in the body, maintain a positive nitrogen balance, thereby promoting fetal growth. In addition, female sex hormones act on the function of the nervous system, mainly through the pituitary-gonadal axis: they affect behavior, stress response, sleep, heart rate, and body temperature.

It is believed that estrogens during gestation have the opposite effect of progesterone. For example, they increase uterine contractility by increasing the excitability of the myometrium through a change in the resting membrane potential and the formation of "gap junctions", and through an increase in the production of prostaglandins.

It is widely believed that estrogens play a fundamental role in regulating the sequence of events leading to childbirth. They potentiate a series of changes, including an increase in the production of prostaglandins G2 and F2, an increase in the expression of prostaglandin receptors, oxytocin receptors, a-adrenergic agonist, modulation of membrane calcium channels, increased synthesis of connexin, regulation of the enzyme responsible for muscle contraction (MLCK). All these changes make it possible to coordinate the contractions of the uterus.

So, during pregnancy, estrogens improve uteroplacental blood flow, promote non-ovascularization of the placenta (for optimal gas exchange and the supply of nutrients necessary for the rapid development of the fetus and placenta). Estrogens affect the production of other steroid and protein hormones, stimulate the work of 11R-hydroxysteroid dehydrogenase in the placenta, regulate the expression of LDL, carry out functional / biochemical differentiation of trophoblast cells, and perform many other functions. Estrogens are thought to play a central, integrating role in modulating dialogue and signaling the placenta-fetus system, leading to the maintenance of pregnancy.

LITERATURE

1. Lutsenko M.T., Samsonov V.P. The main directions and prospects for the development of research work at the Institute of Physiology and Pathology of Respiration of the Siberian Branch of the Russian Academy of Medical Sciences // Bulletin of Physiology and Pathology of Respiration. 1998. Issue 2. S.1-9.

2. Lutsenko M.T. Morphofunctional characteristics of the fetoplacental barrier in herpesvirus infection // Bulletin of the Far Eastern Branch of the Russian Academy of Sciences. 2004. No. 3. S. 155-166.

3. Lutsenko M.T., Andrievskaya I.A. The state of the fetoplacental barrier in case of herpesvirus infection in pregnant women // Siberian Scientific Medical Journal. 2008. Vol.28, No. 5. Pp. 142-147.

4. Albrecht E.D., Babischkin J.S., Pepe G.J. Regulation of placental villous angiopoietin-1 and -2 expression by estrogen during baboon pregnancy // Mol. Reprod. Dev. 2008. Vol.75, No. 3. P.504-511.

5. Albrecht E.D., Henson M.C., Pepe G.J. Regulation of placental low density lipoprotein uptake in baboons by estrogen // Endocrinology. 1991. Vol. 128, No. 1. P.450-458.

6. Albrecht E.D., Pepe G.J. Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy // Int. J. Dev. Biol. 2010. Vol.54, No. 23. P.397-407.

7. Billiar R.B., Pepe G.J., Albrecht E.D. Immunocyto-chemical identification of the estrogen receptor in the nuclei of human placental syncytiotrophoblasts // Placenta. 1997. Vol.18, No. 4. P.365-370.

8. Brandenberger A.W. Tee M.K., Lee J.Y., Chao V., Jaffe R.B. Tissue distribution of estrogen receptors alpha

(ER-alpha) and beta (ERbeta) mRNA in the midgestational human fetus // J. Clin. Endocrinol. Metab. 1997. Vol.82, No. 10. P.3509-3512.

9. Bukovsky A., Caudle M.R., Cekanova M., Fernando R.I., Wimalasena J., Foster J.S., Henley D.C., Elder R.F. Placental expression of estrogen receptor beta and its hormone binding variantcomparison with estrogen receptor alpha and a role for estrogen receptors in asymmetric division and differentiation of estrogen-dependent cells // Re-prod. Biol. Endocrinol. 2003. No. 1. P.36-56.

10. Chen J.Q., Delannoy M., Cooke C., Yager J.D. Mitochondrial localization of ERa and ERp in human MCF7 cells // Am. J. Physiol. Endocrinol. Metab. 2004. Vol.286, No. 6. P. E1011-E1022.

11. Chobotova K., Spyropoulou I., Carver J., Manek S., Heath J.K., Gullick W.J., Barlow D.H., Sargent I.L., Mar-don H.J. Heparin-binding epidermal growth factor and its receptor ErbB4 mediate implantation of the human blastocyst // Mech. Dev. 2002. Vol.119, No. 2. P.137-144.

12. Cronier L., Guibourdenche J., Niger C., Malassine A. Oestradiol stimulates morphological and functional differentiation of human villous cytotrophoblast // Placenta.

1999. Vol.20, Iss.8. P.669-676.

13. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress // Endocr. Rev. 2004. Vol.25, No. 4. P.581-611.

14. Ferrara N, Gerber H.P. The role of vascular en-dothelial growth factor in angiogenesis // Acta Haematol. 2001. Vol.106, No. 4. P.148-156.

15. Irwin R. W., Yao J., Hamilton R., Cadenas E., Brin-ton R.D., Nilsen J. Progesterone and Estrogen Regulate Oxidative Metabolism in Brain Mitochondria // Endocrinology. 2008. Vol.149, No. 6. P.3167-3175.

16. Kota S.K., Gayatri K., Jammula S., Kota S.K., Krishna S.V.S., Meher L.K., Modi K.D. Endocrinology of parturition // Indian J. Endocrinol. Metab. 2013. Vol.17, No. 1. P.50-59.

17. Lippert C., Seeger H., Mueck A.O., Lippert T.H. The effects of A-ring and D-ring metabolites of estradiol on the proliferation of vascular endothelial cells // Life Sci.

2000. Vol.67, No. 13. P.1653-1658.

18. Lobov I.B., Brooks PC, Lang RA. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo // Proc. Natl Acad. Sci. USA. 2002. Vol.99, No. 17. P.11205-11210.

19. Mesiano S. The endocrinology of human pregnancy and fetoplacental neuroendocrine development // Yen and Jaffe "s reproductive endocrinology / J. F. Strauss, R. L. Bar-bieru (eds). Philadelphia, 2009.942 p.

20. Mesiano S., Jaffe R.B. Interaction of insulin-like growth factor-II and estradiol directs steroidogenesis in the human fetal adrenal toward dehydroepiandrosterone sulfate production // J. Clin. Endocrinol. Metab. 1993. Vol.77, No. 3. P.754-758.

21. Miller V.M., Duckles S.P. Vascular Actions of Estrogens: Functional Implications // Pharmacol. Rev. 2008. Vol.60, No. 2. P.210-241.

22. Miller A.A., Drummond G.R., Mast A.E., Schmidt H.H., Sobey C.G. Effect of gender on NADPH-oxidase ac-

tivity, expression, and function in the cerebral circulation: role of estrogen // Stroke. 2007. Vol.38, No. 7. P.2142-2149.

23. Musicki B., Pepe G.J., Albrecht E.D. Functional differentiation of the placental syncytiotrophoblast: effect of estrogen on chorionic somatomammotropin expression during early primate pregnancy // J. Clin. Endocrinol. Metab. 2003. Vol.88, No. 9. P.4316-4323.

24. Nakagawa Y., Fujimoto J., Tamaya T. Placental growth by the estrogen-dependent angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, throughout gestation // Gynecol. Endocrinol. 2004. Vol.19, No. 5. P.259-266.

25. Nevo O., Soustiel J.F., Thaler I. Maternal cerebral blood flow during normal pregnancy: a cross-sectional study. // Am. J. Obstet. Gynecol. 2010. Vol.203, No. 5. P.475e1-e6.

26. Ospina J.A., Duckles S.P., Krause D.N. ^ -Estradiol decreases vascular tone in cerebral arteries by shifting COX-dependent vasoconstriction to vasodilation // Am. J. Physiol. Heart Circ. Physiol. 2003. Vol.285, No. 1. P.241-250.

27. Ospina J.A., Krause D.N., Duckles S.P. ^ -Estradiol increases rat cerebrovascular prostacyclin synthesis by elevating cyclooxygenase-1 and prostacyclin synthase // Stroke. 2002. Vol.33, No. 2. P.600-605.

28. Paech K., Webb P., Kuiper G.G., Nilsson S., Gustafsson J., Kushner P.J., Scanlan T.S. Differential lig-and activation of estrogen receptors ERalpha and ERbeta at AP1 sites // Science. 1997. Vol.277, No. 5331. P.1508-1510.

29. Pepe G.J., Albrecht E.D. Activation of the baboon fetal pituitary-adrenocortical axis at midgestation by estrogen: adrenal A5-3p-hydroxysteroid dehydrogenase and 17a-hydroxylase-17, 20-lyase activity // Endocrinology. 1991. Vol. 128, No. 8. P.2395-2401.

30. Pepe G.J., Burch M.G., Albrecht E.D. Estrogen regulates 11 beta-hydroxysteroid dehydrogenase-1 and -2 localization in placental syncytiotrophoblast in the second half of primate pregnancy // Endocrinology. 2001. Vol. 142, No. 10. P.496-503.

31. Putney D.J., Pepe G.J., Albrecht E.D. Influence of the fetus and estrogen on serum concentrations and placen-tal formation of insulin-like growth factor I during baboon pregnancy // Endocrinology. 1990. Vol. 127, No. 5. P.2400-2407.

32. Ramayya M.S. Adrenal Organogenesis and steroidogenesis: Role of nuclear nuclear receptor steroidogenic factor-1, dax-1, and estrogen receptor // Adrenal disorders / A.N. Margioris, G.P. Chrousos (eds). Totowa, N.J .: Humana Press, 2001.437 p.

33. Reynolds L.P., Redmer D.A. Angiogenesis in the Placenta // Biol. Reprod. 2001. Vol.64, No. 4. P.1033-1040.

34. Rider V., Carlone D.L., Foster R.T. Estrogen and progesterone control basic fibroblast growth factor mRNA in the rat uterus // J. Endocrinol. 1997. Vol.154, No. 1. P.75-84.

35. Rosenthal M.D., Albrecht E.D., Pepe G.J. Estrogen modulates developmentally regulated gene expression in the fetal baboon liver // Endocrine. 2004. Vol.23, No. 2-3.

36. Rubanyi G. M., Johns A., Kauser K. Effect of estrogen on endothelial function and angiogenesis // Vascul. Pharmacol. 2002. Vol.38, No. 2. P.89-98.

37. St-Pierre J. Drori S., Uldry M., Silvaggi JM, Rhee J., Jäger S., Handschin C., Zheng K., Lin J., Yang W., Simon DK, Bachoo R., Spiegelman BM Suppression of reactive oxygen species and eurodegeneration by the PGC-1 transcriptional coactivators // Cell. 2006. Vol. 127, No. 2. P.397-408.

38. Tomooka Y., DiAugustine R., McLachlan J. Proliferation of mouse uterine epithelial cells in vitro // Endocrinology. 1986. Vol.118, No. 3. P.1011-1018.

39. Yang S.H., Liu R., Perez E.J., Wen Y., Stevens S.M. Jr., Valencia T., Brun-Zinkernagel A.M., Prokai L., Will Y., Dykens J., Koulen P., Simpkins J.W. Mitochondrial localization of estrogen receptor ß // Proc. Natl Acad. Sci. USA. 2004. Vol.101, No. 12. P.4130-4135.

40. Yu L., Saile K., Swartz CD, He H., Zheng X., Kissling GE, Di X., Lucas S., Robboy SJ, Dixon D. Differential expression of receptor tyrosine kinases (RTKs) and IGF- I pathway activation in human uterine leiomyomas // Mol. Med. 2008. Vol.14, No. 5-6. P.264-275.

1. Lutsenko M.T., Samsonov V.P. Main research directions and development prospects at the Institute of Physiology and Pathology of Respiration. Bûlleten "fiziologii i patologii dyhaniâ 1999; 2: 1-9 (in Russian).

2. Lutsenko M.T. The morphofunctional description of the fetoplacental barrier under the herpes-viral infection. Vestnik Dal "nevostochnogo otdeleniya Rossiyskoy akademii nauk 2004; 3: 155-166.

3. Lutsenko M.T., Andrievskaya I.A. The State of Fe-toplacental Barrier at Herpes Viral Infection in Pregnant Women. Sibirskiy nauchniy meditsinskiy zhurnal 2008; 28 (5): 142-147 (in Russian).

4. Albrecht E.D., Babischkin J.S., Pepe G.J. Regulation of placental villous angiopoietin-1 and -2 expression by estrogen during baboon pregnancy. Mol. Reprod. Dev. 2008; 75 (3): 504-511.

5. Albrecht E.D., Henson M.C., Pepe G.J. Regulation of placental low density lipoprotein uptake in baboons by estrogen. Endocrinology 1991; 128 (1): 450-458.

6. Albrecht E.D., Pepe G.J. Estrogen regulation of pla-cental angiogenesis and fetal ovarian development during primate pregnancy. Int. J. Dev. Biol. 2010; 54 (2-3): 397-407.

7. Billiar R.B., Pepe G.J., Albrecht E.D. Immunocyto-chemical identification of the estrogen receptor in the nuclei of human placental syncytiotrophoblasts. Placenta 1997; 18 (4): 365-370.

8. Brandenberger A.W. Tee M.K., Lee J.Y., Chao V., Jaffe R.B. Tissue distribution of estrogen receptors alpha (ER-alpha) and beta (ERbeta) mRNA in the midgestational human fetus. J. Clin. Endocrinol. Metab. 1997; 82 (10): 3509-3512.

9. Bukovsky A., Caudle M.R., Cekanova M., Fernando R.I., Wimalasena J., Foster J.S., Henley D.C., Elder R.F.

Placental expression of estrogen receptor beta and its hormone binding variant-comparison with estrogen receptor alpha and a role for estrogen receptors in asymmetric division and differentiation of estrogen-dependent cells. Re-prod. Biol. Endocrinol. 2003.1: 36-56.

10. Chen J.Q., Delannoy M., Cooke C., Yager J.D. Mi-tochondrial localization of ERa and ERp in human MCF7 cells. Am. J. Physiol. Endocrinol. Metab. 2004; 286 (6): E1011-E1022.

11. Chobotova K., Spyropoulou I., Carver J., Manek S., Heath J.K., Gullick W.J., Barlow D.H., Sargent I.L., Mar-don H.J. Heparin-binding epidermal growth factor and its receptor ErbB4 mediate implantation of the human blastocyst. Mech. Dev. 2002; 119 (2): 137-144.

12. Cronier L., Guibourdenche J., Niger C., Malassine A. Oestradiol stimulates morphological and functional differentiation of human villous cytotrophoblast. Placenta 1999; 20 (8): 669-676.

13. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr. Rev. 2004; 25 (4): 581-611.

14. Ferrara N., Gerber H.P. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol. 2001; 106 (4): 148-156.

15. Irwin R. W., Yao J., Hamilton R., Cadenas E., Brin-ton R. D., Nilsen J. Progesterone and Estrogen Regulate Oxidative Metabolism in Brain Mitochondria. Endocrinology 2008; 149 (6): 3167-3175.

16. Kota S.K., Gayatri K., Jammula S., Kota S.K., Krishna S.V.S., Meher L.K., Modi K.D. Endocrinology of parturition. Indian J. Endocrinol. Metab. 2013; 17 (1): 5059.

17. Lippert C., Seeger H., Mueck A.O., Lippert T.H. The effects of A-ring and D-ring metabolites of estradiol on the proliferation of vascular endothelial cells. Life Sci. 2000; 67 (13): 1653-1658.

18. Lobov I.B., Brooks P.C., Lang R.A. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc. Natl Acad. Sci. USA 2002; 99 (17): 11205-11210.

19. Mesiano S. The endocrinology of human pregnancy and fetoplacental neuroendocrine development. In: Strauss J.F., Barbieru R.L. (eds). Yen and Jaffe "s reproductive endocrinology. Philadelphia; 2009.

20. Mesiano S., Jaffe R.B. Interaction of insulin-like growth factor-II and estradiol directs steroidogenesis in the human fetal adrenal toward dehydroepiandrosterone sulfate production. J. Clin. Endocrinol. Metab. 1993; 77 (3): 754-758.

21. Miller V.M., Duckles S.P. Vascular Actions of Estrogens: Functional Implications. Pharmacol. Rev. 2008; 60 (2): 210-241.

22. Miller A.A., Drummond G.R., Mast A.E., Schmidt H.H., Sobey C.G. Effect of gender on NADPH-oxidase activity, expression, and function in the cerebral circulation: role of estrogen. Stroke 2007; 38 (7): 2142-2149.

23. Musicki B., Pepe G.J., Albrecht E.D. Functional differentiation of the placental syncytiotrophoblast: effect of estrogen on chorionic somatomammotropin expression

during early primate pregnancy. J. Clin. Endocrinol. Metab. 2003; 88 (9): 4316-23.

24. Nakagawa Y., Fujimoto J., Tamaya T. Placental growth by the estrogen-dependent angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, throughout gestation. Gynecol. Endocrinol. 2004; 19 (5): 259-266.

25. Nevo O., Soustiel J.F., Thaler I. Maternal cerebral blood flow during normal pregnancy: a cross-sectional study. Am. J. Obstet. Gynecol. 2010; 203 (5): 475. e1-6.

26. Ospina J.A., Duckles S.P., Krause D.N. 17ß-Estra-diol decreases vascular tone in cerebral arteries by shifting COX-dependent vasoconstriction to vasodilation. Am. J. Physiol. Heart Circ. Physiol. 2003; 285 (1): H241-250.

27. Ospina J.A., Krause D.N., Duckles S.P. 17ß-Estra-diol increases rat cerebrovascular prostacyclin synthesis by elevating cyclooxygenase-1 and prostacyclin synthase. Stroke 2002; 33 (2): 600-605.

28. Paech K., Webb P., Kuiper G.G., Nilsson S., Gustafsson J., Kushner P.J., Scanlan T.S. Differential lig-and activation of estrogen receptors ERalpha and ERbeta at API sites. Science 1997; 277 (5331): 1508-1510.

29. Pepe G.J., Albrecht E.D. Activation of the baboon fetal pituitary-adrenocortical axis at midgestation by estrogen: adrenal A5-3ß-hydroxysteroid dehydrogenase and 17a-hydroxylase-17, 20-lyase activity. Endocrinology 1991; 128 (8): 2395-2401.

30. Pepe G.J., Burch M.G., Albrecht E.D. Estrogen regulates 11 beta-hydroxysteroid dehydrogenase-1 and -2 localization in placental syncytiotrophoblast in the second half of primate pregnancy. Endocrinology 2001; 142 (10): 496-503.

31. Putney D.J., Pepe G.J., Albrecht E.D. Influence of the fetus and estrogen on serum concentrations and placen-tal formation of insulin-like growth factor I during baboon pregnancy. Endocrinology 1990; 127 (5): 2400-2407.

32. Ramayya M.S. Adrenal Organogenesis and Steroidogenesis: Role of Nuclear Nuclear Receptor Steroidogenic Factor-1, DAX-1, and Estrogen Receptor. In: Margioris A.N., Chrousos G.P., editors. Adrenal disorders. Totowa, N.J .: Humana Press; 2001: 11-45.

33. Reynolds L.P., Redmer D.A. Angiogenesis in the Placenta. Biol. Reprod. 2001; 64 (4): 1033-1040.

34. Rider V., Carlone D.L., Foster R.T. Estrogen and progesterone control basic fibroblast growth factor mRNA in the rat uterus. J. Endocrinol. 1997; 154 (1): 75-84.

35. Rosenthal M.D., Albrecht E.D., Pepe G.J. Estrogen modulates developmentally regulated gene expression in the fetal baboon liver. Endocrine 2004; 23 (2-3): 219-228.

36. Rubanyi G. M., Johns A., Kauser K. Effect of estrogen on endothelial function and angiogenesis. Vascul. Pharmacol. 2002; 38 (2): 89-98.

37. St-Pierre J. Drori S., Uldry M., Silvaggi JM, Rhee J., Jäger S., Handschin C., Zheng K., Lin J., Yang W., Simon DK, Bachoo R., Spiegelman BM Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 2006; 127 (2): 397-408.

38. Tomooka Y., DiAugustine R., McLachlan J. Prolif-

eration of mouse uterine epithelial cells in vitro. Endocrinology 1986; 118 (3): 1011-1018.

39. Yang S.H., Liu R., Perez E.J., Wen Y., Stevens S.M. Jr., Valencia T., Brun-Zinkernagel A.M., Prokai L., Will Y., Dykens J., Koulen P., Simpkins J.W. Mitochondrial localization of estrogen receptor ß. Proc. Natl Acad. Sci.

USA 2004; 101 (12): 4130-4135.

40. Yu L., Saile K., Swartz CD, He H., Zheng X., Kissling GE, Di X., Lucas S., Robboy SJ, Dixon D. Differential expression of receptor tyrosine kinases (RTKs) and IGF- I pathway activation in human uterine leiomyomas. Mol. Med. 2008; 14 (5-6): 264-275.

Received 03/11/2016

Contact information Inna Viktorovna Dovzhikova, Doctor of Biological Sciences, Leading Researcher, Laboratory of Mechanisms of Etiopathogenesis and Restorative Processes of the Respiratory System

for nonspecific lung diseases, Far Eastern Scientific Center of Physiology and Pathology of Respiration,

675000, Blagoveshchensk, st. Kalinin, 22.

E-mail: [email protected] Correspondence should be addressed to Inna V. Dovzhikova,

PhD, DSc, Leading staff scientist of Laboratory of Mechanisms of Etiopathogenesis and Recovery

Processes of the Respiratory System at Non-Specific Lung Diseases, Far Eastern Scientific Center of Physiology and Pathology of Respiration, 22 Kalinina Str., Blagoveshchensk, 675000, Russian Federation.

Female hormones estrogens play an important role in the body's work: consider the symptoms of their deficiency in young girls and older women, as well as effective methods for correcting endocrine disorders.

Symptoms

Depending on the age of the woman, hypoestrogenism can manifest itself in different ways.

Symptoms of hormone deficiency in young girls

Primary hormone deficiency becomes evident during adolescence. The girl has a delay in sexual development, underdeveloped mammary glands, and the absence of pronounced secondary sexual characteristics. In some cases, the child's figure develops according to the male type, with a narrow pelvis, broad shoulders and prominent muscles.

An important indicator of the normal hormonal background in a girl is menarche. The first menstruation, as a rule, begins at 12-13 years old, and the full cycle is established by the age of 14-16. If there is little estrogen in the body, menstruation may be several years late, and sometimes they are completely absent.

At the reception at the gynecologist, small ("childish") sizes of the uterus and a general underdevelopment of primary and secondary sexual characteristics are noted. Without timely treatment, such a patient will not be able to get pregnant and give birth to a child.

Lack of estrogen in women of reproductive age

The problems that the patient encounters when dealing with absolutely all body systems. This is due to gross metabolic disorders in organs and tissues due to a deficiency of essential biological substances.

Low estrogen is manifested by the following clinical signs:

early aging;

dry skin and mucous membranes;

the formation of wrinkles, acne and other skin problems;

increased fragility of hair and nails;

dysbiosis of the vagina;

frequent colpitis of yeast and other etiology, which are difficult to treat;

decreased libido;

lack of natural vaginal lubrication during sex;

menstrual irregularities - irregular menstruation, scanty bleeding, soreness, amenorrhea;

with concomitant progesterone deficiency - severe premenstrual syndrome;

primary or secondary infertility;

disorders of the central nervous system - frequent headaches, irritability, weakness, impairment of memory and cognitive (cognitive) functions;

bloating, stool disorders;

problems with thermoregulation - the so-called hot flashes, in which a woman is thrown into the heat, then into the cold;

anginal pain;

weight gain despite the safety of the usual diet;

insomnia.

Menopause as a physiological phenomenon

Menopause is a natural process in a woman's life. On average, it develops by the age of 50, but it can occur a little earlier or later (usually between 40 and 55 years).

From about age 35, healthy ovaries begin to gradually decrease the amount of estrogen produced. This process continues until regular menstruation stops and the woman completely loses her fertile function. Although such changes are physiological, they are still a kind of stress for the body. Changes in estrogen levels affect many organs and systems:

MC becomes irregular: the intervals between periods are lengthened, then shortened, the volume of discharge may also be unequal. Spotting in the middle of the cycle is possible.

Hot flashes appear - a feeling of heat waves spreading from the chest area to the neck, arms, face. They occur quite often (up to 20-30 times a day) and last 3-4 minutes. The next attack is often replaced by increased sweating, and then chills.

Dryness in the vagina. During menopause, the vagina becomes less elastic, and its mucous epithelium produces almost no natural lubrication. This can cause great discomfort during intercourse.

A powerful hormonal change is also negatively reflected in the nervous system: many studies have shown the connection between low estrogen and emotional lability, irritability, chronic fatigue, insomnia and other problems.

Weight gain despite the usual diet.

Hypoestrogenism in pregnant women

During pregnancy, the level of estrogen (like some other hormones) increases significantly.

But what happens if there is a lack of sex hormones in the body of the expectant mother? This can lead to:

early miscarriages;

eating disorders and premature placental abruption;

the development of abnormalities in the formation of the fetus;

problems in the work of the heart and central nervous system in a child;

uterine bleeding;

in the later stages - weakness of labor.

What is dangerous

Pathological risks arising from a deficiency of female sex hormones are typical for patients of any sex and age, regardless of the cause of hormonal imbalance.

Complications of estrogen deficiency include:

osteoporosis and high risk of injury;

Chronic pathological processes in the genitourinary system;

Diseases of the circulatory system.

Osteoporosis is a decrease in bone density and abnormal remodeling of bone tissue. It is rather difficult to diagnose pathology at an early stage, so most often doctors are faced with its consequences.

According to statistics, women with a lack of estrogen increase the risk of developing by 30%.

One in five patients with such an injury dies within three months due to complications of prolonged immobilization.

Hypoestrogenism also causes atrophy of the epithelium of the urinary tract. Atrophic urethritis and cystitis are manifested by painful and frequent urination, urgency, urinary incontinence, and recurrent infections. Symptomatic treatment of such pathologies is ineffective, hormonal correction is necessary.

Also, a lack of estrogen is one of the risk factors for the development of CVD diseases.

Patients with a deficiency of female sex hormones are three times more likely to die from acute cardiovascular complications - heart attack and stroke.

Treatment

To make up for the lack of estrogen, the endocrinologist must find out the causes of the pathological condition. In addition, when drawing up an individual therapy plan, the patient's age, individual characteristics, obstetric history and concomitant diseases are taken into account.

Nutrition and lifestyle correction

Curiously, hypoestrogenic therapy often begins with dietary and lifestyle recommendations. It has been proven that the regular use of products such as:

beans, peas, chickpeas, lentils and other legumes;

olives and olives;

vegetables - eggplant, pumpkin, carrots, cabbage, broccoli;

pomegranate, apricots, mango, papaya;

soy products;

pumpkin seeds, sunflower seeds, sesame seeds;

sprouted wheat;

olive and linseed oil.

In addition, for the prevention of osteoporosis, endocrinologists recommend taking foods rich in vitamin D (fatty sea fish, egg yolk, liver, milk) or special therapeutic and prophylactic complexes (for example, Calcium D3 Nycomed, D-calcine).

In addition to diet, regular physical activity, quitting smoking, limiting the use of coffee, salt and sugar will help to normalize hormones. Following the principles of healthy lifestyle significantly reduces the risk of metabolic (metabolic) disorders, reduces the severity of symptoms of hypoestrogenism.

Phytotherapy

On the recommendation of a doctor, you can use infusions and decoctions of herbal phytoestrogens. - This is a heterogeneous group of natural plant compounds that have an effect on the body similar to that of female sex hormones. Among them:

• hibiscus;

  plantain;

• red brush;

• fenugreek;

  boron uterus;

For women of the older age category, who have fulfilled the reproductive function, the intake of medicinal plants is recommended in a continuous mode for 3-5 years. A patient of reproductive age should take phytoestrogens according to the scheme:

herbs with estrogenic action - from 3-5 to 15-18 days of the menstrual cycle;

herbs with a progestogenic effect - from 15-18 to 25-28 days of the menstrual cycle.

This scheme allows you to simulate physiological fluctuations in the level of hormones in the body.

Hormone replacement therapy

In case of severe hormonal disorders, medications are prescribed - analogues of female hormones in the form of tablets, patches, gels, ointments, subcutaneous implants, vaginal suppositories and injections.

In this case, the doctor should be based on the modern principles of HRT:

use only natural estrogens (estradiol valerate, 17β-estradiol, conjugated hormones - Kliogest, Klimen, Divina, Cyclo-proginova);

prescribe the minimum effective dose of hormones;

select the drug individually;

regularly monitor the results of treatment.

The most popular dosage form of hormones is oral tablets. To alleviate the symptoms of urinary tract damage, HRT can be prescribed topically.

Hormone replacement therapy is not used if there are contraindications. Among them:

hormone-dependent tumors of the genital organs;

breast cancer (including a history);

venous thromboembolism;

decompensated kidney and liver diseases;

bleeding from the genital tract of unknown etiology.

Every year HRT is improving. Today, drugs are being studied that activate estrogen receptors, but do not affect breast cell division or the blood coagulation system. In the future, this will make hormone treatment not only effective, but also absolutely safe.

In case of serious emotional and mental disorders, courses of herbal or synthetic drugs that affect the nervous system are additionally prescribed - antidepressants, antipsychotics, drugs for the treatment of insomnia, etc.

Lack of estrogen is not only an unpleasant condition, but also extremely dangerous to health. In addition to the loss of reproductive function, a woman has a marked increase in the risk of developing osteoporosis, atherosclerosis, hypertension, thyroid disorders and other problems. Therefore, it is important to diagnose and treat such a condition in a timely manner. Have you encountered hypoestrogenism? Tell your story in the comments.

The successful course of pregnancy largely depends on the hormonal background of the woman. One of the most important hormones that affect not only the growth and development of the baby, but also provide the necessary changes in the body of the expectant mother is the hormone estrogen. How important is the role of estrogen for a successful pregnancy, read in our article.

Estrogen: the role of a hormone in the body

Estrogens - female sex hormones, are represented by three main types:

• Estron (E1).
• Estradiol (E2).
• Estriol (E3).

Estrogens are called female beauty hormones. They are the ones who turn the girl into a woman. The normal estrogenic background in the body makes the "weaker sex" the owners of a slender waist, rounded hips, velvety skin, beautiful hair, gentle voice, and an object of sex appeal in the eyes of men.

Before pregnancy, the synthesis of these hormones is carried out in a woman's ovaries, adrenal glands and in the adipose tissue of the abdomen, and after conception, the corpus luteum becomes the main source of estrogen, and then the placenta of the growing fetus.

The most active estrogenic species is estradiol. It is this fraction of hormones that is responsible for the growth of female genital organs (uterus, ovaries) and the development of the mammary glands.

In adolescence, estradiol promotes the development of secondary sexual characteristics and the formation of a girl's figure according to the female type. In an adult woman, the hormone is necessary for a normal menstrual cycle, the maturation of the egg and the preparation of the body for future pregnancy.

Estradiol is the most important and active hormone in an adult woman outside of pregnancy.

The weakest estrogen, estriol, is only important during pregnancy. During this period, it is synthesized in very large quantities (1000 times more than before conception) and is an important indicator of a successfully developing fetus. It is detected in blood plasma and urine.

Estrone is a relatively weak estrogen, its activity is 10 times less than estradiol. Its main source is adipose tissue, where it is formed from male hormones, androgens. The concentration of estrone is increased during menopause, when the female body no longer needs active estrogens.

Pregnancy, in order to create comfortable conditions for the developing fetus, "forces" the body to synthesize estrogens in large quantities. Their high concentration is noted in the last weeks of gestation.

It turns out that during pregnancy, the amount of estrogen is produced, which is synthesized in the body of a non-pregnant woman in only 150 years!

So why do you need so much estrogen during pregnancy?

A sufficient content of estrogen in the body of a pregnant woman contributes to:

• growth of the uterus;
• improving blood flow in the uterus and placenta, ensuring the supply of nutrients to the growing fetus;
• the development of the child's lung and bone tissue, as well as his liver and kidneys;
• preparing a woman's body for lactation;
• prevention of postpartum hemorrhage;
• relaxation of the ligamentous apparatus of the pelvic bones and softening of the cervix, which facilitates the passage of the baby through the birth canal.

It should be added that the shine in the eyes of the expectant mother and the special femininity of the pregnant woman are also the merit of estrogens, as well as the appearance of age spots on the skin and edema.

Hormone rates before pregnancy

The level of estradiol in the blood varies during the menstrual cycle. A woman's normal cycle is 28-30 days and is divided into 2 phases. Phase I begins on the 1st day of menstruation and ends with ovulation, which occurs on the 14th day. Phase II follows ovulation and continues until the next menstrual bleeding.

The concentration of hormones in the woman's blood

Outside of pregnancy, the doctor evaluates the work of the ovaries by the level of estradiol. An analysis to determine the hormone is most often prescribed for menstrual irregularities or infertility.

Estrogen rates during pregnancy

The table shows the average data. Hormone levels in different laboratories may differ from these limits.

If the pregnancy is going well, then the level of estriol in the blood increases with each week of pregnancy. A significant increase in the concentration of the hormone begins from the second trimester of pregnancy and continues to increase until the very birth.

When do estrogen levels return to normal after childbirth?

After the birth of a baby, the body no longer requires such a high concentration of estrogen as during gestation. During this period, the activity of another hormone, prolactin, increases, the action of which is aimed at lactation. And the estrogen content decreases 3-4 days after childbirth and returns to normal within a week.

What does a change in the level of the hormone estrogen mean during pregnancy?

Increased synthesis of estriol

Estriol is an indicator of the normal well-being of the fetus and the correct functioning of the placenta. This is the key to a successful pregnancy!

The reasons for an excessive increase in estriol synthesis can be:

• twins, triplets;
• fetal weight over 4 kg;
• rh-conflict pregnancy;
• pathological weight gain (adipose tissue is a source of estrogen).

The detection of estriol above the average in the above conditions should not cause alarm in the expectant mother.

Decreased synthesis of estriol

A low concentration of estriol or its absence indicates "poor" work of the placenta and is a sign of fetal distress.

What leads to very low estriol content?

1. Down syndrome.
2. Fetal malformations.
3. Intrauterine infection.
4. Taking corticosteroids for the expectant mother.
5. Fetal death (while the synthesis of the hormone is sharply reduced, by more than 50%).

Reasons for an insufficient increase in estriol levels:

1. Kidney pathology in a pregnant woman.
2. Anemia.
3. Poor or inadequate nutrition.
4. Hypertension or diabetes mellitus.
5. Preeclampsia and eclampsia.
6. Fetal growth retardation syndrome.
7. Oxygen starvation of the fetus.

What to do?

The increase in the amount of estriol during pregnancy and its peak before childbirth is a physiological condition. This is an indicator that the fetus is healthy, growing and developing! High estriol levels do not require correction.

The female body is controlled by estrogen hormones. Without them, a woman cannot be feminine, become pregnant, and safely bear a baby. Even if the expectant mother had no problems with the estrogen saturation of the body before conception, she needs to monitor the hormonal background during pregnancy and conduct a blood or urine test to determine the level of estriol - a very important indicator of the fetus's well-being. For the reliability of the result, do not limit yourself to a single diagnosis, but repeat the analysis 2-3 times. So a pregnant woman can be sure that the concentration of estriol naturally increases and nothing threatens her baby.

Biologically active compounds are called hormones. They affect human health and psyche. Many hormones during pregnancy are activated and support the mother's body, help the fetus develop and create a strong bond between them. All processes and reactions are adjusted to the new position. Some hormones come into play, others fade into the background.

Hormones are involved in metabolism, they provide vital processes and growth of the body. These substances are produced by the glands that make up the human endocrine system. The endocrine glands are located in different parts of the body and affect different processes.

Major glands:

• the pituitary gland is located in the brain, it controls other glands, the pituitary hormones determine the size of a person and the intensity of growth processes;
• the thyroid gland is located in the cervical region, its hormones are involved in the metabolism;
• the parathyroid glands are located near the thyroid gland, they allow regulating the synthesis of calcium and phosphorus;
• the thymus, or thymus gland, located in the upper part of the chest, produces thymosin, which helps in building the immune system;
• the pancreas secretes juice for digesting food, as well as insulin, which regulates carbohydrate metabolism;
• the adrenal glands produce substances that are involved in metabolism and maintain the functionality of the nervous system, the gland also produces sex hormones;
• the pineal gland or pineal gland is located in the brain, produces melatonin, which regulates the daily regimen;
• the gonads are responsible for reproduction, their hormones develop secondary sexual characteristics (in girls, the shape of the skeleton and pelvis changes, the mammary glands enlarge, the figure is outlined, pubic and armpit hair appears, menstruation occurs, reproductive function is established).

Why you need to check your hormonal background

Hormones are involved in all basic body processes: growth, development, metabolism, reproduction. For the body to function properly, the hormone ratio must be appropriate for the person's sex and age. There are norms for each hormone and each individual category of people.

Each indicator is important for a pregnant woman. Any changes in the analyzes reflect the development of the fetus. That is why the doctor regularly monitors hormones. Various methods are used to study hormonal levels.

Perinatal screening is mandatory - a group of studies that help determine the risk of developing defects in the fetus. Doctors recommend screening at least twice. In the first trimester, studies are carried out at 11-12 weeks. In the second trimester, 16-19 weeks are suitable.

In women, the hormonal background changes after puberty, at the time of conception, during menopause. A routine laboratory blood test can detect many diseases and even determine the localization and nature of the abnormalities. A blood test for hormones is an important part of the examination of a pregnant woman. Based on their results, the gynecologist can assess the condition of the mother and child and draw up the correct treatment plan.

What tests are taken for hormones during pregnancy

Since the chemical composition of hormones varies, there are different ways to study blood. During pregnancy, tests for pituitary hormones may be needed:

• prolactin;
• thyroid-stimulating hormone.

Sex hormone tests:

• estriol;
• testosterone.

Analysis for adrenal hormones:

• cortisol;
• adrenocorticotropic hormone;
• DHEA sulfate.

Thyroid hormone test:

• thyroid-stimulating (TSH);
• triiodothyronine (T3);
• triiodothyronine (free T3);
• thyroxine (T4);
• free thyroxine (free T4).

Antibody test:

• thyroglobulin;
• thyroid peroxidase.

These hormones are studied in perinatal screening in the first and second trimesters. In the first trimester, the level of PAPP-A and beta-hCG is measured. The second examines AFP, E3 and hCG hormones. It is also necessary to control 17-ketosteroids and 17-hydroxyprogesterone, as well as globulin, which binds sex hormones. In parallel, analyzes are carried out for hormones of the reproductive system (testosterone, estradiol) and the adrenal gland substance cortisol.

Human chorionic gonadotropin (hCG)

Closer to the 10th week of pregnancy, the placenta begins to vigorously produce hormones. produced by the membrane of the fetus (chorion). The secretion begins immediately after the embryo is attached to the inner layer of the uterus. HCG is one of the most important hormones for humans, especially for maintaining pregnancy. This hormone controls the production of other substances necessary for pregnancy - progesterone and estrogen.

In a healthy pregnancy, hCG levels rise steadily. By 10-11 weeks, the concentration of the hormone in the blood decreases and does not change until delivery. With a lack of hCG, a miscarriage occurs: progesterone does not sufficiently prepare the endometrium, the egg does not hold and leaves the uterus, menstruation occurs.

It is the hCG hormone that confirms pregnancy. A simple test reacts to the hormone in the urine as early as 5-6 days after conception, however, it is more reliable to conduct a blood test. The hCG level makes it possible to calculate the period when a woman cannot accurately determine the day of conception.

HCG indicators reflect the condition of the fetus, so the analysis allows you to find out about complications. For each gestational age, the rate of hCG in the blood has been established, which confirms the correct development of the fetus.

Abnormal growth of hCG can indicate multiple pregnancies, diabetes mellitus, gestosis (microdamage of the placenta). Sometimes an increase in hormone levels indicates malformations and hereditary diseases such as Down syndrome.

A decrease in hCG occurs with an ectopic pregnancy, as well as a frozen one. This can be a manifestation of developmental delay, placental insufficiency (violation of the functionality of the placenta), spontaneous abortion.

With high or low hCG levels, you don't need to be intimidated. Perhaps the date of conception was incorrectly indicated.

Placenta hormones

Progesterone

During a certain period of the menstrual cycle, progesterone levels rise. The hormone is produced by the corpus luteum, which matures at the site of the follicle after it releases an egg on the day of ovulation.

This hormone is responsible for the readiness of the uterus for implantation, it is considered the main one during pregnancy. Progesterone promotes better attachment of the fertilized egg to the endometrium of the uterus. The hormone prevents miscarriage by reducing the tone of the uterus.

Conception does not occur without normal progesterone levels. The hormone sends signals to the central nervous system to prepare for conception. It preserves the pregnancy and creates the necessary conditions for carrying and feeding the baby. Progesterone also worries about the psychological state of a woman. It calms the pregnant woman, creates affection and love for the fetus.

On the other hand, progesterone affects the psyche, making a woman irritable and depressed. Also, the hormone retains salts and fluids, causes headaches, drowsiness, nausea, and increases urination. Thanks to progesterone, the mammary glands swell and hurt.

The concentration of progesterone doubles by week 8, and increases gradually by week 38. In the first trimester, 9 nmol / L is considered the norm and an increase to 770 nmol / L by the third trimester.

Lack of progesterone is associated with pregnancy complications. It is possible to replenish hormone reserves with medication. Otherwise, the pregnancy ends in miscarriage or underdevelopment.

Placental lactogen

Placental lactogen levels determine the risk of chromosomal abnormalities. The hormone is secreted by the placenta. It is present in the woman's blood from 5-6 weeks. Normally, the maximum placental lactone in the blood is observed at 37-38 weeks. After this period, the level of the hormone drops.

The study of the level of placental lactogen is aimed at assessing the state of the placenta. The analysis allows you to diagnose failure in time. A sharp decline in the hormone twice or more (in comparison with normal indicators on a certain day of pregnancy) may indicate a delay in the development of the child. A decrease in the level of placental lactogen by 80% can lead to fetal death. The doctor should notice the drop in time to urgently prevent the reduction of the hormone.

The norm of placental lactogen is 0.05 mg / l in the early stages with an increase to 11.7 by 40 weeks. The analysis for lactogen is carried out in the presence of two history of miscarriages.

Estrogens

The level of estrogen is also important during pregnancy. The hormone supports labor and helps the uterus grow. Also, estrogens normalize blood pressure, remove fluid, relax blood vessels. Estrogens are produced by the baby's placenta and adrenal glands.

Free estriol improves blood circulation in the vessels of the uterus. The hormone affects the mammary glands, helps the body adapt to feeding the baby. The analysis for free estriol reveals placental insufficiency (impaired blood supply to the placenta), developmental delay, post-term pregnancy. At 5-6 weeks of gestation, the rate of estriol is 0.6-2.5 nmol / l. By week 40, the level of the hormone rises to 111 nmol / l.

Ovarian hormones

At normal times (estrogen) is produced by the ovaries, and after conception also by the placenta. It maintains the normal course of pregnancy, so its level is constantly increasing. First, an estradiol test can tell you about the condition of the placenta. A reduction in estradiol early in pregnancy may indicate a risk of termination of pregnancy.

In the first week, the norm is 800-1400 pmol / l, and in the last week 57100-99100 pmol / l. Immediately before childbirth, the level of estradiol increases to the maximum. It is he who needs to say thanks for relieving pain during childbirth, since estradiol is a natural pain reliever.

On a psychological level, estradiol is responsible for the readiness for a baby. The hormone affects the woman, and she begins to buy things, equip the room and prepare for the birth of a child.

If you have a history of miscarriages, you need to monitor progesterone and estradiol both before conception and after. It is necessary to monitor the state of the hormonal background even during preparation for fertilization, as it affects the implantation and development of the fetus.

Adrenal hormones

Pituitary adrenocorticotropic hormone (ACTH) stimulates the production of mineralocorticoids and glucocorticoids by the adrenal glands. Under stress, the level of ACTH increases and the secretion of adrenal hormones increases. Pregnancy is such stress.

Influence of adrenal hormones:

• suppression of immunity, prevention of fetal rejection;
• regulation of water-salt balance through the retention of salts and fluids;
• weakening of hair;
• formations of stretch marks (stretch marks);
• hyperpigmentation of the skin;
• strong hair growth.

Thyroid hormones

During pregnancy, it is necessary to monitor the functionality of the thyroid gland. Insufficiency and excessive production of hormones by this organ can cause malformations in the fetus. The state of the thyroid gland can be assessed by thyroxine and triiodothyronine.

An analysis for hormones during pregnancy of this gland is prescribed to those patients who have problems with the organ in history. The indication can be severe fatigue, drowsiness, problems with hair, skin and nails, low blood pressure, swelling and a sharp increase in weight. All of these signs may indicate thyroid dysfunction.

Failure is often diagnosed during pregnancy, although an excess of thyroid hormones is also possible (hyperthyroidism). An excess is dangerous for premature birth. Launched hypothyroidism (lack of hormones) leads to fetal death in the womb, mental retardation.

It is necessary to research such hormones:

• thyroid stimulating hormone (TSH), which stimulates the secretion of thyroid hormones (the norm is 0.4-4.0 mU / l, in pregnant women the norm is 0.4-2.0 mU / l);
• free thyroxine (free T4), which accelerates metabolism (the norm is 9-22 pmol / l, during pregnancy 8-21 pmol / l);
• triiodothyronine (free T3), which also speeds up metabolism, but is more active (the norm is 2.6-5.7 pmol / l, during pregnancy, the indicators remain normal).

Sometimes the endocrinologist also prescribes a test for antibodies to thyroglobulin (AT-TG) and thyroperoxidase (AT-TPO) - proteins that appear in the blood during inflammation of the gland.

Pituitary hormones

In the process of fetal growth, hormones from the pituitary gland, an endocrine gland located in the brain, are also involved. During childbirth, the uterus contracts under the influence of oxytocin. Postpartum lactation is due to prolactin. Lack of prolactin reduces the amount of breast milk.

Oxytocin and prolactin are the so-called maternity hormones. They help a woman feel love for her baby, feel like a mother and enjoy feeding. These hormones tell a woman how to behave, how to prioritize. Nature, through hormones, makes a woman, like any female on the planet, to love and protect her child. Thus, the procreation and preservation of each population is carried out.

The desire of a woman to be close to her child and to protect him depends on the concentration of the hormones of motherhood. The concentration of motherhood hormones changes gradually so that the woman's psyche can prepare for the appearance of a baby.

The hormonal system reacts sharply to external stimuli and internal changes. Therefore, a blood test for hormones during pregnancy is taken in the morning on an empty stomach. A few days before the procedure, you need to refrain from physical and emotional stress, exclude alcohol and cigarettes.

It must be remembered that the hormonal background primarily depends on the woman's mood. Its importance for the development of a healthy pregnancy is great, but almost any hormone can be replenished with medication. Therefore, do not panic if the analysis shows an excess or lack of an active substance.

The intensity of the positive as well as negative effects of the growth of hormones during pregnancy depends on many factors: heredity, health, mood, individual characteristics.

Placenta like the corpus luteum, it secretes estrogens and progesterone. Histochemical and physiological studies show that these two hormones, along with most other placental hormones, are produced by syncytial trophoblastic cells of the placenta.

The figure shows that as you approach the end of pregnancy the daily production of placental estrogens increases by almost 30 times compared with the initial level. However, the secretion of estrogen by the placenta differs from that by the ovaries: the estrogens secreted by the placenta are not re-secreted from the main substrates in the placenta, but almost all are formed from the androgenic steroid hormones dehydroepiandrosterone and 16-hydroxydehydroepiandrosterone, which are secreted both by the maternal adrenal glands and the adrenal glands. These weak androgens are transported by the blood to the placenta and are converted by trophoblast cells into estradiol, estrone and estriol (the adrenal cortex of the fetus is extremely large and almost 80% consists of the so-called detailed zone, the main function of which, apparently, is the secretion of dehydroepiandrosterone during pregnancy).

Functions of Estrogen During Pregnancy... Earlier, when discussing estrogens, we indicated that these hormones mainly affect the proliferative functions of the reproductive and functionally related organs of the maternal organism. During pregnancy, huge amounts of estrogen cause: (1) an increase in the size of the uterus; (2) enlargement of the mammary glands and the growth of milk ducts in them; (3) enlargement of the female external genitalia.

Estrogens also cause relaxation of the maternal pelvic ligaments, which increases mobility in the sacroiliac joint and makes the symphysis of the pubic bones more elastic. These changes make it easier for the fetus to pass through the birth canal. There is reason to believe that estrogens also affect many important aspects of fetal development during pregnancy, for example, the rate of cell division during early embryonic development.

Apparently progesterone no less than estrogens, it is important for a successful pregnancy. In addition to the amount of progesterone that is moderately produced by the corpus luteum at the beginning of pregnancy, it is synthesized in large quantities later by the placenta. The secretion of progesterone increases approximately 10 times during pregnancy.

There are special influences progesterone the normal course of pregnancy.
1. Progesterone causes the development of decidual cells in the endometrium of the uterus, which play an important role in the nutrition of the embryo in the early stages of embryonic development.
2. Progesterone reduces the contractility of the pregnant uterus, which prevents contractions that could cause spontaneous abortion.

3. Progesterone promotes the development of the zygote even before implantation. specifically increases the secretory processes in the fallopian tubes and uterus, which provides nutrients to the developing morula and blastocyst. There is also reason to believe that progesterone affects the processes of cell division in the early stages of embryonic development.
4. The progesterone secreted during pregnancy helps estrogen prepare the mammary glands for lactation.