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Endocrinology Vol. 143, No. 6 2189-2197
Copyright © 2002 by The Endocrine Society


NEUROENDOCRINOLOGY

Genistein Affects ERß- But Not ER{alpha}-Dependent Gene Expression in the Hypothalamus

Heather B. Patisaul, Melissa Melby, Patricia L. Whitten and Larry J. Young

Center for Behavioral Neuroscience (H.B.P., P.L.W., L.J.Y.), Department of Anthropology (M.M., P.L.W.), and Department of Psychiatry and Behavioral Sciences (L.J.Y.), Emory University, Atlanta, Georgia 30329

Address all correspondence and requests for reprints to: Heather B. Patisaul, Ph.D., Center for Behavioral Neuroscience, Emory University, 954 Gatewood Road Northeast, Atlanta, Georgia 30329. E-mail: hbeaupr{at}emory.edu.

Isoflavone phytoestrogens are growing increasingly popular because of their reported cardiovascular and anticarcinogenic properties, but the effects of these compounds in the brain are largely unknown. In a previous study, we found that an isoflavone supplement, containing a mixture of soy phytoestrogens, inhibited estrogen-dependent female sexual behavior and was antiestrogenic for both ER{alpha}- and ERß-dependent gene expression in the hypothalamus. Here we examined the impact of the soy isoflavone genistein, a major component of the supplement, on estrogen-dependent female sexual behavior and ER{alpha}- and ERß-dependent gene expression in the rat brain. Genistein, at a dietary concentration of 100 or 500 ppm had no effect on lordosis behavior in rats. However, at 500 ppm genistein had differential activity through ER{alpha} and ERß in the hypothalamus. Genistein had no effect, in either the presence or absence of 17ß-E2, on oxytocin receptor density in the ventromedial nucleus of the hypothalamus, an estrogen-dependent action thought to be regulated via ER{alpha}. However, genistein increased ERß mRNA expression in the paraventricular nucleus of the hypothalamus by 24%, whereas 17ß-E2 decreased ERß mRNA expression by 26%, a process likely mediated by ERß itself. These results suggest that at this dose, genistein has antiestrogenic action through ERß in the paraventriculr nucleus but negligible activity through ER{alpha} in the brain.




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