This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mesiano, S. Articles by Jaffe, R. B. Search for Related Content PubMed PubMed Citation Articles by Mesiano, S. Articles by Jaffe, R. B.

Phytoestrogens Alter Adrenocortical Function: Genistein and Daidzein Suppress Glucocorticoid and Stimulate Androgen Production by Cultured Adrenal Cortical Cells¹

Reproductive Endocrinology Center, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143-0556

Address all correspondence and requests for reprints to: Robert B. Jaffe, M.D., Reproductive Endocrinology Center, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143-0556. E-mail: robert_jaffe{at}quickmail.ucsf.edu

Phytoestrogens influence a variety of biological processes. As 17ß-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 µmol/L) decreased ACTH-stimulated cortisol production to basal levels (ED₅₀, 1–4 µmol/L). In the adult adrenocortical cell line, H295, genistein, daidzein, and 17ß-estradiol (10 µmol/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 µmol/L). In H295 cells, basal and cAMP-stimulated DHEA production were similarly increased by the phytoestrogens and 17ß-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.

This article has been cited by other articles:

				M. S. Baquedano, N. Saraco, E. Berensztein, C. Pepe, M. Bianchini, E. Levy, J. Goni, M. A. Rivarola, and A. Belgorosky Identification and Developmental Changes of Aromatase and Estrogen Receptor Expression in Prepubertal and Pubertal Human Adrenal Tissues J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2215 - 2222. [Abstract] [Full Text] [PDF]

				Y.-C. Chen, M. L Nagpal, D. M Stocco, and T. Lin Effects of genistein, resveratrol, and quercetin on steroidogenesis and proliferation of MA-10 mouse Leydig tumor cells J. Endocrinol., March 1, 2007; 192(3): 527 - 537. [Abstract] [Full Text] [PDF]

				B. L. Dillingham, B. L. McVeigh, J. W. Lampe, and A. M. Duncan Soy Protein Isolates of Varying Isoflavone Content Exert Minor Effects on Serum Reproductive Hormones in Healthy Young Men J. Nutr., March 1, 2005; 135(3): 584 - 591. [Abstract] [Full Text] [PDF]

				J Liu, X-D Li, A Ora, P Heikkila, A Vaheri, and R Voutilainen cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-{alpha} in NCI-H295R adrenocortical cells J. Mol. Endocrinol., October 1, 2004; 33(2): 511 - 522. [Abstract] [Full Text] [PDF]

				M. Cifuentes, J. P. Advis, and S. A. Shapses Estrogen Prevents the Reduction in Fractional Calcium Absorption Due to Energy Restriction in Mature Rats J. Nutr., August 1, 2004; 134(8): 1929 - 1934. [Abstract] [Full Text] [PDF]

				C. E. Wood, J. M. Cline, M. S. Anthony, T. C. Register, and J. R. Kaplan Adrenocortical Effects of Oral Estrogens and Soy Isoflavones in Female Monkeys J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2319 - 2325. [Abstract] [Full Text] [PDF]

				E. Kallay, H. Adlercreutz, H. Farhan, D. Lechner, E. Bajna, W. Gerdenitsch, M. Campbell, and H. S. Cross Phytoestrogens Regulate Vitamin D Metabolism in the Mouse Colon: Relevance for Colon Tumor Prevention and Therapy J. Nutr., November 1, 2002; 132(11): 3490S - 3493. [Abstract] [Full Text] [PDF]

				S. A. Whitehead, J. E. Cross, C. Burden, and M. Lacey Acute and chronic effects of genistein, tyrphostin and lavendustin A on steroid synthesis in luteinized human granulosa cells Hum. Reprod., March 1, 2002; 17(3): 589 - 594. [Abstract] [Full Text] [PDF]

				H. Nejaty, M. Lacey, and S. A. Whitehead Differing Effects of Endocrine-Disrupting Chemicals on Basal and FSH-Stimulated Progesterone Production in Rat Granulosa-Luteal Cells Experimental Biology and Medicine, June 1, 2001; 226(6): 570 - 576. [Abstract] [Full Text] [PDF]