Estrogens
Female sex hormones (estradiol, estriol, folliculin) produced by follicles in the ovaries, placenta, in small amounts – adrenal cortex and testes. There are three main estrogens: b-estradiol, estriol, and estrone. They are derivatives of estrane (C-18 steroids):
The ovaries and placenta are the main organs producing estrogens in a woman’s body. 17b-estradiol (E2) is the main ovarian estrogen. It is 12 times more active than estrone and 80 times more than estriol. Other female sex hormones – estrone (E1) and estriol (E3) are synthesized not in the ovaries from b-estradiol. The central link of estrogen biosynthesis is the aromatization of androgens. Three hydroxylation reactions take place, involving O2 and NADPH. This aromatization complex includes mixed function P450 oxidase. If testosterone is the substrate of this complex, estradiol is formed, if androstenedione – estrone (the process does not occur in the ovaries).
Estrogen biosynthesis in the ovaries
A significant amount of estrogens are also formed in peripheral tissues by aromatizing androgens. In the male body, about 80% of estradiol (E2) is formed in this way. In women, the main source of estrogens is adrenal cortex androgens.
The secretion of hormones synthesized in the ovaries depends on the phase of a woman’s menstrual cycle and the intensity of hormone biosynthesis. Estrogens are not accumulated but are immediately excreted.
Estrogens and gestagens, like other steroid hormones, bind to plasma transport proteins. Estrogens bind to sex hormone-binding globulin, while gestagens bind to corticosteroid-binding globulin.
In the liver, estradiol and estrone are converted into estriol. Estradiol, estriol, and estrone in the liver are converted into glucuronides and sulfates. The formed compounds are soluble but do not bind to transport proteins, so they are easily excreted with bile, feces, slightly harder – with urine. The most important compounds are estrone and 2-hydroxyestrone glucuronides and estransulfates, formed by esterification at C-3. Sulfate can also attach to C-17, forming 3,17-estradiol disulfate. The mechanism of action of female sex hormones is similar to that of steroid hormones. Estrogens interact with receptors in target cells located in the skin, bones, muscles, and reproductive organs.
Estrogens and gestagens act through intracellular receptors to which these hormones bind.
The main function of estrogens is to prepare a woman’s reproductive organs for reproductive activity. This is related to preparing the reproductive organs, controlling ovulation, fertilization, blastocyst implantation, regulating pregnancy, childbirth, and lactation.
– When estrogens act, DNA and RNA and protein synthesis are activated. They promote the formation of reproductive organs, the growth and differentiation of uterine tissues, vaginal epithelium, the growth of uterine and mammary gland tissues, vascularization, and cell division.
– By increasing the activity of ornithine decarboxylase, estrogens activate putrescine formation, which promotes the formation of polyribosomes and regulates protein synthesis.
– Estrogens regulate the formation of secondary sexual characteristics during puberty, the formation of vocal cords, mammary glands. The sexual instinct and psychological perception of women are formed.
– By binding to uterine muscle cell receptors, estrogens inhibit their Na+, K+-ATPase. Sodium is retained, along with water, potassium is lost. This causes depolarization, increases uterine muscle excitability, and strengthens contractions.
– Estrogens activate the metabolism of fats, especially phosphoglycerides, in reproductive organs, promote the synthesis of low and high-density lipoproteins in the liver, reduce cholesterol concentration in the blood. They promote fat accumulation in the skin, mammary glands, pelvic, and buttocks area.
– By acting on estrogens, the epiphyseal growth plates of bones calcify, improve calcium absorption in the intestines, and increase its concentration in the blood. They increase calcitonin secretion. This leads to increased bone mass, improved bone structure, and increased strength.
– Estrogens (especially during pregnancy) intensify ceruloplasmin biosynthesis and regulate copper concentration in the blood.
– Estrogens dilate peripheral blood vessels and increase heat dissipation.
Gestagens. The most important representative is progesterone, which is synthesized (from cholesterol) in the corpus luteum, placenta, seminal vesicles, and adrenal glands. In women with a normal menstrual cycle, the main source of progesterone is the corpus luteum, and during pregnancy – the placenta (from the sixth week of pregnancy it secretes up to 250 mg per day). Progesterone in the blood binds to corticosteroid-binding globulin (~18%) and albumin (80%). About 2% is free.
In the liver, progesterone is converted into pregnandiol, which forms pregnandiol glucuronides eliminated in the urine.
Progesterone is an intermediate product in the biosynthesis of corticosteroids, androgens, and estrogens. The half-life of progesterone is 6 minutes. Its metabolism is indicated by the amount of pregnandiol excreted in the urine.
Oral progesterone is inactive because it is rapidly inactivated in the liver into several compounds. Sodium pregnandiol-20-glucuronide is the main metabolite of gestagens in the urine.
Some synthetic steroids (e.g., 17a-hydroxyprogesterone, 19 – derivatives of nortestosterone) have hormonal activity, but they are not metabolized in the liver, so they are used as oral contraceptives.
Progesterone is an antagonist of estrogens. High concentrations suppress ovulation, so during pregnancy, when the body produces a lot of progesterone, ovulation does not occur. Progesterone cell targets are in the reproductive organs and mammary glands. Their cytoplasmic receptors consist of A (M – 110,000) and B (M – 117,000) components. The formed complex of progesterone and the receptor binds specifically to nuclear proteins. Progesterone can also bind to androgen receptors, hence a certain androgenic effect. When estrogens act, the number of progesterone receptors increases.
Progesterone’s effect during the luteal phase:
· progesterone regulates gene transcription and enhances the synthesis of corresponding RNA proteins;
· suppresses contractions of uterine smooth muscles and fallopian tubes, reduces sensitivity to oxytocin;
· gestagens, by reducing estrogen-induced stimulation of vaginal epithelium, activate the transition of uterine epithelium from the growth phase to the secretory phase, increasing the size of secretory glands and accumulating glycogen, necessary for the implantation of a fertilized egg;
· progesterone is necessary for the course of pregnancy, promotes the development of mammary glands and lactation;
· gestagens, by slowing peripheral circulation, reduce heat loss, so during the luteal phase of the menstrual cycle, the temperature rises by about 0.5 °C; this temperature surge is a sign of ovulation;
· progesterone acts immunosuppressively on the mother’s immune system and protects the fetus from the effects of antigens;
· progesterone suppresses ovulation. This is the basis for the use of synthetic gestagens as contraceptives.
Source | Glossary of Most Commonly Used Biomedical Terms and Concepts | Lithuanian University of Health Sciences | Academician Professor Antanas Praškevičius, Professor Laima Ivanovienė