In this article we will discuss about Estrogen. After reading this article you will learn about: 1. Meaning of Estrogen 2. Source of Estrogen 3. Biosynthesis 4. Transport 5. Catabolism 6. Control.

Meaning of Estrogen:

Estrogen is a kind of female sex-steroid hor­mone. It plays a great role in reproductive physiology. Estrogen is a generic term for a substance that induces reproductive cycle. Allen and Doisy (1923) first identified the major source of estrogenic activity in female.

Chemically estrogens are derivatives of a C18 hydrocarbon.

Three compounds of this group with hormonal activity are:

(a) β-estradiol (E2) – C18H24O2

(b) Estriol-C18H24O3

(c) Estrone (E1)- C18H22O2

All these are characterized by the ab­sence of a CH3 group at Carbon 10 and by the aromatic nature of ring A, making the OH group phenolic in character. Of all these β-estradiol (E2) is the most potent physiologi­cally, estrone (E,) less potent and Estriol is least active. The relative potencies are 50:5:1 respectively (Fig. 6.12).

Principal Estrogens

Source of Estrogen:

Estrogen is secreted from the theca interna and granulosa cells of graafian follicle of ovary. Interstitial cells, adrenal cortex, tes­tis and placenta also secrete trace amount of estrogen.

Biosynthesis of Estrogen:

Estrogens are a family of hormones synthe­sized in a variety of tissues. 1 7p-estradiol (E2) is the primary estrogen of ovarian hormone. Cholesterol is the precursor of estrogen bio­synthesis. Cholesterol is metabolised to preg­nenolone by P450 cleaved enzyme. Pregnenolone is then converted to progesterone in presence of enzymes 3β-OHSD and ∆5,4 isomerase. Within the ovarian follice, test­osterone is formed either from progesterone or from pregnenolone like testosterone bio­synthesis.

Estrogens are formed by aromatization of androgens in a complex process that in­volves 3 hydroxylation steps each of which required O2 and NADPH. The aromatase enzyme complex is thought to include a P450 mixed function oxidase. 1 7β-estradiol (E2) is primarily formed from testosterone. Estradiol is readily oxidized to estrone (E1) in the liver; estrone may be further hydrated to estriol (Fig. 6.13).

Biosynthesis of Estrogens

There are different ideas of estrogen syn­thesis:

1. Two-cell-theory:

This theory states that the thecal cells produce C19 androgens by the stimulation of LH. C19 androgens are then delivered to the granulosa cells where they are aromatized to estrogens. It is also observed that granulosa cells of several species secrete estrogens after stimulation of FSH. Thecal cells produce large amount of androgens. The CYP17 gene that codes for 1 7-hydroxylase and C17-20 Lyase is actively regulated by LH.

Granulosa cells have little or no capac­ity to produce C19 androgens but have an active aromatase system (Fig. 6.14).

Two-Cell Theory of Estrogen Synthesis

2. Modified theory:

A modified two-cell- theory states that LH stimulates andro­gen production within the thecal cells. Androgens are then aromatized within the thecal cells but are also made avail­able to the granulosa cells for aromatization to estrogens. Estrogens of thecal cells origin would be the major source of circulating levels of steroid where as estrogens synthesized by granulosa cells would serve a local role, probably help in ovum maturation.

Transport of Estrogen:

Estrogens are bound to Sex Hormone Bind­ing Globulin (SHBG) and transported through plasma.

Catabolism of Estrogen:

Estrogens are excreted in the bile and urine in conjugation with glucuronides and sul­fates.

Control of Estrogen:

Adenohypophysial gonadotropin level con­trols the synthesis of estrogen during repro­ductive cycle.

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