Physiology of the ovaries

Ovaries perform a generative function, i.e., they are the place of formation of oocytes and sex hormones that have a wide spectrum of biological action.

Dimensions average 3-4 cm in length, 2-2.5 cm in width, 1-1.5 cm in thickness. The consistency of the ovary is dense, the right ovary is usually somewhat heavier than the left one. In color they are whitish-pink, matte. Without a peritoneal cover, the ovaries are surrounded from the outside by a single layer of cubic epithelial cells, often called the embryo. Below it there is an albuginea, which is a connective tissue hard capsule. Under it is located the cortex (cortex), which is the main germinative and hormone-producing part of the ovaries. In it among the connective tissue stroma lie the follicles. Their main mass is the primordial follicles, which are an ovum, surrounded by a single layer of follicular epithelium.

The reproductive period of life is characterized by cyclic changes in the ovary: the maturation of the follicles, their rupture with the release of the mature egg, ovulation, the formation of the yellow body and its subsequent involution (in the case of not becoming pregnant).

The hormonal function of the ovary is an important link in the endocrine system of the female body, on which the normal functioning of both the sexual organs and the entire female body depends.

A distinctive feature of the functioning of reproductive processes is their rhythm. The main content of female sexual cycles is reduced to hormone-dependent changes in two processes that determine the optimal conditions for reproduction: the willingness of the female body for sexual intercourse and fertilization of the egg and ensuring the development of a fertilized egg. The cyclical nature of reproductive processes in females is largely determined by the sexual differentiation of the hypothalamus according to the female type. Their main meaning lies in the presence and active functioning of two female centers for the regulation of gonadotropin (cyclical and tonic) ejection in adult females.

The duration and nature of cycles in females of various mammalian species is very different and genetically fixed. In humans, the cycle duration is often 28 days; It is accepted to divide into two phases: follicular and lutein.

In the follicular phase, the growth and maturation of the basic morphofunctional unit of the ovaries - the follicle, which is the main source of formation of estrogens - occurs. The process of growth and development of follicles in the first phase of the cycle is strictly determined and described in detail in the literature.

The rupture of the follicle and the release of the egg cause the transition to the next phase of the ovarian cycle - luteal, or the phase of the yellow body. The cavity of the burst follicle quickly grows granulosa cells resembling vacuoles, which are filled with a yellow pigment - lutein. There is an abundant capillary network, as well as trabeculae. Yellow cells of teca interna produce mainly progestins and a certain amount of estrogens. In humans, the phase of the yellow body lasts about 7 days. The progesterone secreted by the yellow body temporarily inactivates the positive feedback mechanism, and the secretion of the gonadotropins is controlled only by the negative effect of 17β-estradiol. This leads to a decrease in the level of gonadotropins in the middle of the phase of the yellow body to the minimum values.

Regression of yellow bodies is a very complex process, influenced by many factors. Researchers pay attention primarily to low levels of pituitary hormones and reduced sensitivity to luteal cells. An important role is given to the functions of the uterus; one of its main humoral factors, stimulating luteolysis, are prostaglandins.

The ovarian cycle in women is associated with changes in the uterus, tubes and other tissues. At the end of the luteal phase, there is a rejection of the mucous membrane of the uterus, accompanied by bleeding. This process is called menstruation, and the cycle itself is menstrual. It is considered to be the beginning of the first day of bleeding. After 3-5 days, endometrial rejection stops, bleeding stops, and regeneration and proliferation of new layers of endometrial tissue begins - the proliferative phase of the menstrual cycle. In the most common 28-day cycle in women on the 16-18th day, the proliferation of the mucous membrane is suspended, and it is replaced by the secretory phase. Its beginning coincides in time with the onset of the functioning of the yellow body, the maximum activity of which falls on the 21-23 day. If the egg is not fertilized and implanted before 23-24, the level of progesterone secretion gradually decreases, the yellow body regresses, the secretory activity of the endometrium decreases, and a new cycle begins on the 29th day from the beginning of the previous 28-day cycle.

Biosynthesis, secretion, regulation, metabolism and mechanism of action of female sex hormones. According to the chemical structure and biological function, they are not homogeneous compounds and are divided into two groups: estrogens and gestagens (progestins). The main representative of the first - 17 beta-estradiol, and the second - progesterone. Estrogen also includes estrone and estriol. The hydroxyl group of 17 beta-estradiol is located in the beta position, while the progestins in the beta position are located in the side chain of the molecule.

The starting compounds for the biosynthesis of sex steroids are acetate and cholesterol. The first stages of the biosynthesis of estrogens are similar to the biosynthesis of androgens and corticosteroids. At the biosynthesis of these hormones, the central place is occupied by pregnenolone, formed as a result of cleavage of the side chain of cholesterol. Beginning with pregnenolone, two biosynthetic pathways of steroid hormones are possible: Δ ⁴ - and Δ ⁵ -paths. The first occurs with the participation of Δ ⁴ -3-keto compounds through progesterone, 17α-hydroxyprogesterone and androstenedione. The second involves the successive formation of pregnenolone, 17beta-hydroxypregnenolone, dehydroepiandrosterone, Δ ⁴ -androstendiola testosterone. It is believed that the D-pathway is the main one in the formation of steroids in general. These two ways end in the biosynthesis of testosterone. Six enzyme systems participate in the process: cleavage of the side chain of cholesterol; 17a-hydroxylase; Δ ⁵ -3 beta-hydroxysteroid dehydrogenase with Δ ⁵ - Δ ⁴ isomerase; C17C20-lyase; 17β-hydroxysteroid dehydrogenase; Δ ^5,4- isomerase. The reactions catalyzed by these enzymes occur mainly in microsomes, although some of them may be in other subcellular fractions. The only difference between the microsomal enzymes of steroidogenesis in the ovaries is their localization within the microsomal subfractions.

The final and distinctive stage of the synthesis of estrogen is the aromatization of Cig-steroids. As a result of aromatization of testosterone or Δ ⁴ -androstenedione, 17β-estradiol and estrone are formed. This reaction is catalyzed by the enzyme complex (aromatase) of microsomes. It is shown that the intermediate stage in the aromatization of neutral steroids is hydroxylation in the 19th position. It is the limiting reaction of the whole process of aromatization. For each of the three successive reactions - the formation of 19-hydroxyandrostenedione, 19-ketoandrostenedione and estrone, there is a need for NADPH and oxygen. The aromatization involves three oxidase reactions of a mixed type and is dependent on cytochrome P-450.

During the menstrual cycle, the secretory activity of the ovaries changes from the estrogen in the follicular phase of the cycle to progesterone - in the phase of the yellow body. In the first phase of the cycle granulosa cells do not have blood supply, they have weak 17-hydroxylase and C17-C20-lyase activity, and the synthesis of steroids in them is poor. At this time, significant isolation of estrogens is carried out by cells of teca interna. It is shown that after ovulation in the cells of the yellow body with a good blood supply, an increased synthesis of steroids begins, which, due to the low activity of these enzymes, stops at the progesterone stage. It is also possible that predominates in the follicle Δ ⁵ -path synthesis with little formation of progesterone, and granulosa cells, and in the corpus luteum has been increasing conversion of pregnenolone Δ ⁴ -path, t. E. In progesterone. It should be emphasized that in the interstitial cells of the stroma there is a synthesis of C19-androgen-type steroids.

The place of formation of estrogens in the female body during pregnancy is also the placenta. The biosynthesis of progesterone and estrogens in the placenta is characterized by a number of features, the main of which is that this organ can not synthesize steroid hormones de novo. Moreover, recent literature data indicate that the steroid-producing organ is the placenta-fetus complex.

The determining factor in the regulation of the biosynthesis of estrogens and progestins is gonadotropic hormones. In concentrated form it looks as follows: FSH determines the growth of follicles in the ovary, and LH - their steroid activity; synthesized and secreted estrogens stimulate the growth of the follicle and increase its sensitivity to gonadotropins. In the second half of the follicular phase, the secretion of ovarian estrogen increases, and this increase is determined by the concentration of gonadotropins in the blood and the intragenic ratios of the resulting estrogens and androgens. Having reached a certain threshold value, estrogens by the mechanism of positive feedback contribute to the ovulatory release of LH. Synthesis of progesterone in the yellow body is also controlled by luteinizing hormone. The inhibition of follicular growth in the postovulatory phase of the cycle is probably due to the high intrathecal concentration of progesterone and also androstenedione. Regression of the yellow body is an obligatory moment of the next sexual cycle.

The content of estrogens and progesterone in the blood is determined by the stage of the sexual cycle (Figure 72). At the beginning of the menstrual cycle in women, the concentration of estradiol is about 30 pg / ml. In the second half of the follicular phase, its concentration increases sharply and reaches 400 pg / ml. After ovulation, a drop in the level of estradiol with a slight secondary rise in the middle of the luteal phase is observed. The ovulatory rise of unconjugated estrone averages 40 pg / ml at the beginning of the cycle and 160 pg / ml in the middle. The concentration of the third estrogen estriol in the plasma of non-pregnant women is low (10-20 pg / ml) and rather reflects the metabolism of estradiol and estrone than ovarian secretion. The speed of their production at the beginning of the cycle is about 100 μg / day for each steroid; in the luteal phase, the production rate of these estrogens is increased to 250 μg / day. The concentration of progesterone in peripheral blood in women in the preovulant phase of the cycle does not exceed 0.3-1 ng / ml, and its daily production is 1-3 mg. During this period, its main source is not the ovary, but the adrenal gland. After ovulation, the concentration of progesterone in the blood increases to 10-15 ng / ml. The speed of its production in the phase of the functioning yellow body reaches 20-30 mg / day.

Metabolism of estrogens occurs in an excellent way from other steroid hormones. A characteristic feature for them is the preservation of the aromatic ring A in estrogen metabolites, and hydroxylation of the molecule is the main way of their transformation. The first stage of the metabolism of estradiol is its transformation into estrone. This process occurs in virtually all tissues. Hydroxylation of estrogens is more likely to occur in the liver, resulting in the formation of 16-hydroxy derivatives. Estriol is the main estrogen of urine. Its main mass in blood and urine is in the form of five conjugates: 3-sulfate; 3-glucuronide; 16-glucuronide; 3-sulfate, 16-glucuronide. A certain group of estrogen metabolites are their derivatives with an oxygen function in the second position: 2-hydroxyestrone and 2-methoxyestrone. In recent years, researchers are paying attention to the study of 15-oxidized derivatives of estrogens, in particular, on 15a-hydroxy derivatives of estrone and estriol. There are other estrogen metabolites, 17a-estradiol and 17-epiestriol. The main ways to remove estrogenic steroids and their metabolites in humans are bile and kidneys.

Progesterone metabolism occurs as Δ ⁴ -3-ketosteroids. The main ways of its peripheral metabolism are the restoration of the A ring or the restoration of the side chain in the 20th position. The formation of 8 isomeric pregnanediols is shown, the main one being pregnanediol.

In studying the mechanism of action of estrogens and progesterone, one should first of all proceed from the positions of ensuring the reproductive function of the female body. Specific biochemical manifestations of the controlling effect of estrogenic and gestagenic steroids are very diverse. First of all, estrogens in the follicular phase of the sexual cycle create optimal conditions that ensure the possibility of fertilization of the oocyte; after ovulation, the main changes are in the structure of the genital tract tissues. There is a significant proliferation of epithelium and keratinization of its outer layer, hypertrophy of the uterus with an increase in the ratio of RNA / DNA and protein / DNA, rapid growth of the mucous membrane of the uterus. Estrogens support certain biochemical parameters of secret secreted into the lumen of the genital tract.

Progesterone of the yellow body ensures successful implantation of the egg in the uterus in case of its fertilization, development of decidual tissue, postimplantation development of the blastula. Estrogens and progestins guarantee the preservation of pregnancy.

All of the above facts indicate the anabolic effect of estrogens on protein metabolism, especially on target organs. In their cells, there are special protein receptors, which determine selective uptake and accumulation of hormones. A consequence of this process is the formation of a specific protein-ligand complex. Achieving nuclear chromatin, it can change the structure of the latter, the level of transcription and the intensity of the synthesis of cellular proteins de novo. Receptor molecules have a high affinity for hormones, selective binding, limited capacity.

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