Phytoestrogens alter adrenocortical function: genistein and daidzein suppress glucocorticoid and stimulate androgen production by cultured adrenal cortical cells.
Phytoestrogens influence a variety of biological processes. As 17beta-estradiol alters adrenocortical cell function, we examined whether the dietary phytoestrogens, genistein and daidzein, have related effects. In cultured human fetal and postnatal adrenal cortical cells, genistein and daidzein (both 0.4-40 micromol/L) decreased ACTH-stimulated cortisol production to basal levels (ED50, 1-4 micromol/L). In the adult adrenocortical cell line, H295, genistein, daidzein, and 17beta-estradiol (10 micromol/L) decreased cAMP-stimulated cortisol synthesis in a similar fashion. Neither genistein nor daidzein altered basal or ACTH-stimulated dehydroepiandosterone sulfate (DHEA-S) production in fetal adrenocortical cells, whereas in postnatal adrenocortical cells, DHEA and DHEA-S were markedly increased (ED50, 1-4 micromol/L). In H295 cells, basal and cAMP-stimulated DHEA production were similarly increased by the phytoestrogens and 17beta-estradiol. Genistein and daidzein did not affect the expression of steroid-metabolizing enzymes. However, genistein and daidzein specifically inhibited the activity of 21-hydroxylase (P450c21); the activities of other steroidogenic enzymes were not affected. Thus, phytoestrogens may decrease cortisol synthesis by suppressing the activity of P450c21 and, as a consequence, increase DHEA/DHEA-S synthesis by shunting metabolites away from the glucocorticoid synthetic pathway. Therefore, consumption of foods containing phytoestrogens may alter adrenocortical function by decreasing cortisol and increasing androgen production.
Reproductive Endocrinology Center, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143-0556, USA.
S
S
Mesiano
S L
SL
Katz
J Y
JY
Lee
R B
RB
Jaffe
D000302:Adrenal Cortex / Q000187:drug effects* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000728:Androgens / Q000096:biosynthesis*; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D005333:Fetus; D019833:Genistein / Q000494:pharmacology*; D005938:Glucocorticoids / Q000096:biosynthesis*; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D007529:Isoflavones / Q000494:pharmacology* / Q000633:toxicity; D048789:Phytoestrogens; D028321:Plant Preparations; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013255:Steroid 21-Hydroxylase / Q000037:antagonists & inhibitors
D000728:Androgens; D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D005938:Glucocorticoids; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; C004742:daidzein; D000324:Adrenocorticotropic Hormone; D019833:Genistein; D000242:Cyclic AMP; D013255:Steroid 21-Hydroxylase; D011505:Protein-Tyrosine Kinases; D006854:Hydrocortisone