Genistein-Induced Histomorphometric and Hormone Secreting Changes in the Adrenal Cortex in Middle-Aged Rats

The soybean phytoestrogen, genistein, is increasingly consumed as an alternative therapeutic for age-related diseases, namely cardiovascular conditions, cancer and osteoporosis. Besides estrogenic/antiestrogenic action, this isoflavone exerts a prominent inhibitory effect on tyrosine kinase and the steroidogenic enzyme families, thus affecting hormonal homeostasis. The aim of this study was to examine the effects of genistein on: histomorphometric features of the adrenal cortex, blood concentrations of aldosterone, corticosterone and dehydroepiandrosterone (DHEA) and adrenal tissue corticosterone content in orchidectomized middle-aged male rats. Sixteen-month-old Wistar rats were divided into sham-operated (SO), orchidectomized (Orx) and genistein-treated orchidectomized (Orx+G) groups. Genistein (30 mg/kg/day) was administered subcutaneously for three weeks, while the control groups received the vehicle alone. The adrenal cortex was analysed histologically and morphometrically. Circulating concentrations of aldosterone, corticosterone and DHEA, as well as adrenal tissue corticosterone levels, were determined by immunoassay. When compared to the SO group, orchidectomy decreased the ZG and ZR cell volume by 43% and 29%, respectively (P < 0.05). Serum concentrations of aldosterone and DHEA were markedly lower [13% and 41%, respectively (P < 0.05)], while serum and adrenal tissue levels of corticosterone did not change after orchidectomy. Orchidectomy followed by genistein treatment increased the ZG, ZF and ZR cell volume by 54%, 34% and 77%, respectively (P < 0.05), compared to the untreated orchidectomized group. Histological analysis revealed noticeable vacuolization of the ZG and ZF cells in the Orx+G group. Serum aldosterone and corticosterone concentrations together with adrenal tissue corticosterone were 47%, 31% and 44% lower, respectively (P < 0.05), whereas serum DHEA concentration was 342% higher (P < 0.05) in this group in comparison with the Orx group. This study shows that in orchidectomized middle-aged rats, genistein can cause the shunting of metabolic pathways in the adrenals, supporting DHEA secretion and inhibiting corticosterone and aldosterone secretion. Exp Biol Med 234:148-156, 2009