Estrogen production in men and post-menopausal women

(1) For men and postmenopausal women, the major sources of estrogen are via aromatization at peripheral sites other than the gonads (E.g. skin, fat, muscle) from circulating androgens.

A woman's  ovaries cease production of estrogens as a result of complete loss of primordial follicles,  however, estrogens continue to be synthesized, at ~ 40-60% of pre-menopausal levels at these sources.

Circulating Androgens ➔  Estrogens

-   Unlike the ovaries and testes, which can synthesize their own androgen precursors, these sites are totally dependent on circulating androgens for conversion to estrogens.    Such androgens are produced by the adrenal cortex, ovarian stroma (especially in post-menopausal women with endometrial cancer, possibly mediated by LH and INSULIN), and testis Leydig cells;

-    Estrogen produced at peripheral sites is probably only biologically active in local tissue.   This is where the aromatase enzyme is produced to convert circulating androgens (ANDROSTENEDIONE in women) to estrogen in tissues containing aromatase, which include:

•   Adipose tissue (mesenchymal cells).   This is a major source of estrogen in men (also the brain) and  the major source in post-menopausal women, thus the amount of body fat significantly determines the amount of estrogen produced and stored; the breasts contain significant amounts of adipose tissue;

Tests show that a fat lady after menopause makes more estrogen than a skinny lady before menopause

Androgens ➔ Estrogens

•   Skin.    The majority of peripheral estrogen production is in the skin

Hall G, Phillips TJ. Estrogen and skin. The effects of estrogen, menopause, and hormone replacement therapy on the skin. J Am Acad Dermatol 2005;53:555-68.

•   Osteoblasts and osteoclasts in bone

•   Vascular endothelial and aortic smooth muscle cells

•   Brain.   Including medial preoptic/anterior hypothalamus, the medial basal hypothalamus and the amygdale

•   Fetal liver

(2)Small amounts are produced in the male testes

-  Stimulated by LH, Lehdig cells produce androgens (TESTOSTERONE, ANDROSTENEDIONE, DHEA) as substrates for FSH-stimulated production and secretion of ESTRADIOL and ESTRONE (via aromatase enzyme) by the Sertoli cells (but less ESTRADIOL  is produced than by a woman's ovaries).     Only ~20% of the substrate TESTOSTERONE is secreted by the testes' Lehdig cells.

-   FSH also increases the Leydig cells response to LH by increasing the number of LH receptors expressed on Leydig cells.

Hemsell DL et al, Plasma precursors of estrogen II. Correlation of the extent of conversion of plasma ANDROSTENEDIONE to ESTRONE with age. J. of Clin End. And Met, 1974;

Longcope Christopher etal, The secretion of ESTRONE and ESTRADIOL-17βby human testis, Elsevier Science Inc., 1972

(3) To a lesser extent, estrogen can be derived from its storage form ESTRONE sulfate (E1S)

 Tissues can draw on E1S as needed.

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