Synthesis of estrogens in the body

Natural estrogens are C18 steroids with an aromatic ring and a hydroxyl group of the third carbon atom.

There are three physiologically important estrogens: estrone (E1), which has a keto group at the C-17 position (Fig. 9-4); Estradiol (E2), which has hydroxyl groups at the positions C-3 and C-17 (Fig. 9-4); And estriol (E3) with hydroxyl groups at the positions C-3, C-16 and C-17. These estrogens are often referred to as E1, E2 and E3, respectively, with signatures denoting the numbers of the hydroxyl groups bound to the steroid ring. In a non-pregnant adult female, estradiol is the main ovarian steroid. Ovary secretes twice as much estradiol as estrone, and estrone has only ten percent estrogenic activity with respect to estradiol. Estriol - the least active of the three indicated estrogens and in non-pregnant women is formed only with the metabolic degradation of estrone and estradiol. The placenta, however, produces significant amounts of estriol, so this hormone plays an important role in pregnancy.

The immediate precursors of estrone and estradiol are the androgen androstenedione and testosterone (Fig. 9-4). Consequently, the pathway for the synthesis of estrogens is similar, in essence, to the synthesis of testicular androgens. Synthesis begins with the cleavage of the side chain of cholesterol with the formation of pregnenolone in the mitochondria. The primary source of cholesterol is probably, apparently, circulating lipoproteins, rather than the synthesis of de novo from acetate. As in all steroid-synthesizing tissues, cleavage of the side chain of cholesterol is a limiting stage in the synthesis of a hormone under hormonal control. Pregnenolone formed in the mitochondria migrates to the endoplasmic reticulum, where it is converted into androgens according to the delta-4 or delta-5 mechanism. The decisive stage in the synthesis of estrogen is the aromatization of the A-ring with simultaneous removal of the methyl group of the C-19 position. This transformation is catalyzed by the enzyme aromatase, it requires NADPH and O2, it occurs in the smooth endoplasmic reticulum. The activity of aromatase is under hormonal control; Thus, both the first and the last stages of the synthesis of estrogen are regulated.

It was found that both envelope cells and granular cells are involved in the production of estrogen. Granular cells are able to synthesize progesterone, but can not convert progesterone into androgens. Thus, although granular cells have a high level of aromatase activity, they are unable to synthesize estrogens until they are provided with androgens as a substrate. In contrast, sheath cells actively produce androgens, but have significantly lower aromatase activity. Shell cells can synthesize a certain amount of estrogens, but most of the estrogens secreted by preovular follicles are probably synthesized by granular cells from the androgens provided by the tissue of the membrane. The involvement of both envelope cells and granular cells in the synthesis of estrogens has important properties for the hormonal regulation of this process.

Ovary is the primary source of circulating estradiol, but plasma estrone is also supplied from a number of other sources. In addition to the ovaries, the adrenal cortex secretes a certain amount of estrone, a significant amount of this estrogen is formed as a result of the aromatization of androstenedione in other tissues. Fatty tissue is the main area of ‚Äč‚Äčthis transformation and can become a clinically important source of estrone in obese women. The ovarian follicle also secrete a number of other steroids, including 17alpha-hydroxyprogesterone and several androgens. The main androgen of the ovaries is androstenedione, but the adrenal glands are a more important source of this androgen in women.