Estrogen and phytoestrogen predispose to erectile dysfunction: do ER-alpha and ER-beta in the cavernosum play a role?

To investigate the functional changes in rabbit penile corpus cavernosum (CC) secondary to experimental hyperestrogenism and attempt to identify sites of immunoexpression for estrogen receptor subtypes alpha and beta (ER-alpha and ER-beta) in the CC. Although the role of testosterone in sexual function has been extensively studied in clinical settings and experimental animal models, the effect of hormonal modulation/imbalance arising from estrogenic excess has not been characterized. Eighteen New Zealand white male rabbits (2.5-3.0 kg) were divided into control and two treatment groups. The two treatment groups were given orally 0.1 mg of estradiol valerate (estradiol group) or phytoestrogen, daidzein (phytoestrogen group) daily for 12 weeks. Blood and tissue samples were collected for hormone levels and in vitro pharmacologic studies. CC samples from untreated rabbits (n = 4) were cryosectioned and incubated with appropriate mouse monoclonal antibody for identification of ER-alpha and ER-beta. Through immunohistochemistry, color signals for nuclear ER-alpha and ER-beta receptors were localized within the CC. Chronic treatment with estradiol and phytoestrogen significantly reduced the systemic total testosterone levels. In organ bath experiments, relaxant responses to acetylcholine, nitroglycerin, and nitrergic transmission were significantly attenuated compared with the control response. With regard to the contractile effect, both types of estrogen treatments significantly potentiated norepinephrine-induced antierectile contraction of the CC. These results indicate that estradiol treatment and chronic exposure of phytoestrogen may cause receptor-mediated pathophysiologic changes in erectile function, leading to erectile dysfunction.