Effects of exogenous melatonin on sex steroid receptors in the ovary, oviduct and uterus and the ovarian oxidative stress in adult UChB rats (10% (v/v) ethanol voluntary intake) during ovulation

Author(s)

Luiz Gustavo de Almeida Chuffa

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2011-10-27

Examining board members

Francisco Eduardo Martinez; Valéria Helena Alves Cagnon; Evanisi Teresa Palomari; José Maria Soares Junior; Renato Simões Cordeiro

• Advisor: Francisco Eduardo Martinez

Abstract

Chronic ethanol intake is associated with female reproductive disturbances including hormonal dysfunction, changes in the steroid receptors expression, production of reactive oxygen species (ROS), among others. Melatonin, an indolamine secreted by pineal gland, plays key roles in the reproductive cycle, besides having an important function in scavenging ROS. Studies focusing chronic alcoholism and its interaction with melatonin, in females, are still inconclusive. This study aims to investigate the effects of exogenous melatonin administration on sex hormones, sex steroid receptors (AR, ER-?, ER-?, PRA and PRB) in the ovary, oviduct and uterus, as well as the nutritional profile and oxidative stress in the ovaries of adult UChB rats (10% (v/v) ethanol voluntary intake). 60 UChB female rats were divided into the following groups: UChB Co: without access to ethanol (used as control); UChB EtOH: drinking daily ethanol at 4 - 5 g ethanol/100g body weight (BW), both receiving vehicle solution. Concomitantly, UChB Co + M and UChB EtOH + M groups received daily injections of melatonin (100?g/100g BW) via i.p, starting from 90 days old and during the next 60 consecutive days. At 150 days of age, all animals were euthanized in estrus (4a.m). Melatonin increased progesterone, 6- sulfatoximelatonin and decreased 17?-estradiol, while the ethanol+melatonin combination caused a significant fall in these hormones. Despite androgen receptor (AR) in ovary has not been influenced by melatonin, ethanol and ethanol+melatonin led to a decrease in oviduct AR. Both estrogen receptors (ER-? and ER-?) were underexpressed by either ethanol or melatonin in oviduct and only uterine ER-? was downregulated. Conversely, progesterone receptors (PRA and PRB) were positively regulated in the ovary by ethanol or ethanol+melatonin, whereas PRA was downregulated in uterus and oviduct, except when ethanol+melatonin were combined. Additionally, melatonin receptor (MT1R) was increased in ovary and uterus of melatonin-treated rats, regardless of ethanol consumption. Body weight gain was reduced with ethanol plus melatonin after 40 days of treatment. In both melatonin-treated groups, it was observed a reduction in food-derived calories and liquid intake toward the end of treatment. The amount of consumed ethanol dropped during the treatment. Estrous cycle was longer in rats that received both ethanol and melatonin, with prolonged diestrus. Following to oxidative status, lipid hydroperoxide levels were higher in the ovaries of ethanol-preferring rats and decreased after melatonin treatment. Additionally, antioxidant activities of superoxide dismutase, glutathione peroxidase and glutathione reductase were increased in melatonin-treated groups . We conclude that melatonin has opposite effect on sex hormones to those of ethanol consumption. Together, melatonin and ethanol differentially regulates the sex steroid receptors in the reproductive tissues, mostly acting "in situ" through its MT1R receptor. Finally, melatonin is able to affect feed efficiency and, conversely, it protects the ovaries against the oxidative stress arising from ethanol consumption. (AU)