Estrogen Production Site Chart

Reproductive

Age Women

ESTRADIOL

(E2)

(17-beta ESTRADIOL)

(circulating hormone)

Ovaries

(granulosa cells)

FSH

▪ ESTRADIOL functions as a circulating hormone (acting on distant target tissues) - Most abundant and potent natural form of estrogen in non-pregnant females during reproductive years.

▪ANDROSTENEDIONE from ovarian theca cells or adrenal cortex is principal substrate for production of ESTRADIOL in ovarian granulosa cells.

Men

and Women

ESTRONE

(E1)

/ESTRADIOL

(E2)

(Localized metabolism)

Adipose tissue

(mesenchymal cells)

Bone (chondrocytes, osteoblasts)

Skin Fibroblasts

Gluco-corticoids;

Class 1 Cytokines

▪ESTRONE (E1) is less abundant than E2 and E3 - but the only one of the 3 present in any quantity in and post-menopausal women ;

▪Adipose and Skin cell aromatization is the major source for circulating ESTRADIOL in men and post-menopausal women -adrenal ANDROSTENEDIONE(a derivative of PROGESTERONE )is converted by aromatase to ESTRONE (E1), which is converted to ESTRADIOL by 17βhydroxysteroid dehydrogenase (17β-HSD) activity.

▪ ESTRONE is a reservoir for ESTRADIOL - ESTRONE is converted to a long-lived storage derivative, calledESTRONEsulfate, which can be converted as needed to the more active ESTRADIOL. ESTRONE is weaker than ESTRADIOL.

▪ Adipose tissue is the greatest peripheral source of aromatase in both males and females contributing to ESTRADIOL production.

▪ESTRONE acts locally at production sites - Circulating estrogensare escapees from local metabolism from such as adipose tissue, brain and bone; Thus low circulating estrogen levels in postmenopausal women and men have little bearing on concentrations in estrogen-producing tissues. E.g. the estrogen responsible for a breast tumor (has up to 10x circulation levels), brain (cognitive) functions, or bone mineralization is that produced locally at those sites.

Brain;

Vascular endothelium;

Aortic smooth muscle

ESTRADIOL (E2)

(Circulating hormone)

Adrenal Cortex

▪ Secretes small amounts of ESTRADIOL;

▪ Adrenal cortex also supplies ANDROSTENEDIONE for conversion to ESTRONE/ESTRADIOL in extragonadal sites.

Men

ESTRADIOL (E2)

ESTRONE (E1)

(Circulating hormone)

Testes

(Leydig cells, Sertoli cells)

FSH

▪ Responsible for at most 15-20% of total circulating ESTRADIOL;

▪Lehdig cells convert TESTOSTERONE (produced by testes' Sertoli cells) ➔  ESTRADIOL to direct spermagenesis

http://erc.endocrinology-journals.org/cgi/reprint/6/2/131.pdf

Pregnancy

ESTRIOL

(E3)

Placenta

Retinoids

▪Only produced in significant amounts by the placenta during pregnancy