Long-Term Exogenous Melatonin Regulates the Expression of Androgen, Estradiol and Progesterone Receptors in the Ovary, Oviduct and Uterus of Ethanol-Preferring Rats.

Abstract

Chronic ethanol intake is associated with female hormonal dysfunction and it is well known that melatonin, an indolamine used for several therapies, plays key roles in regulating reproductive physiology. However its effects via sex steroid hormonal receptors remain inconclusive. Thus, this study was to evaluate how long-term melatonin exerts its regulatory effects on sex steroid receptors in ovary, oviduct and uterus of UChB rats chronically-exposed to ethanol (submitted to 10% (v/v) voluntary ethanol consumption). Forty adult female rats (n = 10/group) were finally selected for this study. UChB Co: drinking water only; UChB EtOH: drinking ethanol at 2-6 mL/100 g/day + water, both receiving 0.9% NaCl + 95% ethanol 0.04mL as vehicle. Concomitantly, UChB Co+M and UChB EtOH+M groups were infused with vehicle + melatonin [100 µg/100 g body weight/day] intraperitoneally for 60 days. All animals were euthanized by decapitation during the morning estrus (4 a.m.) and samples of ovaries, oviducts and uteri were collected and processed for western blot analysis of the melatonin receptor (MT1R), androgen receptor (AR), estrogen receptors (ER-α and ER-β) and progesterone receptors (PRA and PRB). Despite ovary AR has not been influenced by melatonin, both ethanol and ethanol + melatonin led to a decrease in oviduct AR levels, while only ethanol induced lower uterus AR compared to controls. Both ER-α and ER-β were underexpressed by either ethanol or melatonin in both ovary and oviduct and only ER-β showed low expression in uterus of the UChB EtOH and UChB Co+M rats. Conversely, PRA and PRB in the ovary were positively regulated by ethanol or ethanol + melatonin, whereas PRA was suppressed in uterus and oviduct, except when ethanol + melatonin were combined. Additionally, in melatonin-treated rats, regardless of ethanol consumption, there was an increase in ovary and uterus MT1R levels, in contrast to down-regulation of oviduct MT1R mediated by melatonin itself. We conclude that there are interactions between melatonin and ethanol on the expression pattern of androgen, estradiol and progesterone receptors in the ovary, oviduct and uterus of ethanol-preferring rats. Moreover, the responsiveness to androgen receptor is variable, enhancing or attenuating the ethanol effects in the ovary. Melatonin also potentiates the ethanol effects on oviduct and uterus. (poster)