Regulation of estrogen receptor beta mRNA in the brain:: opposite effects of 17β-estradiol and the phytoestrogen, coumestrol

Estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) are differentially distributed in the brain and likely mediate different estrogen-dependent processes. ER beta is abundant in the bed nucleus of the stria terminalis, medial preoptic nucleus, paraventricular nucleus of the hypothalamus and the amygdala of the rat. In the paraventricular nucleus, which is devoid of ER alpha, ER beta is colocalized with the neuropeptides, oxytocin and vasopressin, suggesting a potential functional role for ERP in the regulation of these peptides. We examined the regulation of ER beta mRNA expression in the rat brain by 17 beta-estradiol and the phytoestrogen, coumestrol. 17 beta-Estradiol treatment decreased ER beta mRNA in situ hybridization signal by 44.5% in the paraventricular nucleus of the hypothalamus (PVN), but had no effect in the bed nucleus of the stria terminalis (BnST) or the medial preoptic nucleus (MPA). In contrast, dietary exposure to coumestrol increased ER beta mRNA signal by 47.5% in the PVN but had no effect in the BnST or the MPA. These data demonstrate that like ER alpha ER beta is down regulated by estrogen in a region specific manner in the rat brain. Furthermore, exposure to coumestrol may modulate ER beta-dependent processes by acting as an anti-estrogen at ER beta. This data contradicts results from cell transfection assays which suggest an estrogenic activity of coumestrol on ER beta, indicating that the mode of action may be tissue specific, or that metabolism of dietary coumestrol may alter its effects, Because the highest concentrations of phytoestrogens are found in legumes, vegetables and grains, they are most prevalent in vegetarian and traditional Asian diets. Understanding the neuroendocrine effects of phytoestrogens is particularly important now that they are being marketed as a natural alternative to estrogen replacement therapy and sold in highly concentrated pills and powders. (C) 1999 Elsevier Science B.V. All rights reserved.