Melatonin and ethanol intake exert opposite effects on circulating estradiol and progesterone and differentially regulate sex steroid receptors in the ovaries, oviducts, and uteri of adult rats

•Melatonin and ethanol increase circulating E2 and P4 levels but not other reproductive hormones.•Melatonin and ethanol promoted differential regulation of AR, ER and PR subunits.•MT1R was up-regulated in ovarian and uterine tissue after melatonin–ethanol combination.

Chronic ethanol intake is associated with sex hormone disturbances, and it is well known that melatonin plays a key role in regulating several reproductive processes. We report the effects of ethanol intake and melatonin treatment (at doses of 100 μg/100 g BW/day) on sex hormones and steroid receptors in the ovaries, oviducts and uteri of ethanol-preferring rats. After 150 days of treatment, animals were euthanized, and tissue samples were harvested to evaluate androgen, estrogen, progesterone and melatonin receptor subunits (AR, ER-α and ER-β, PRA, PRB and MT1R, respectively). Melatonin decreased estradiol (E2) and increased progesterone (P4) and 6-sulfatoxymelatonin (6-STM), while an ethanol–melatonin combination reduced both P4 and E2. Ovarian AR was not influenced by either treatment, and oviduct AR was reduced after ethanol–melatonin combination. Oviduct ER-α, ER-β and uterine ER-β were down-regulated by either ethanol or melatonin. Conversely, ovarian PRA and PRB were positively regulated by ethanol and ethanol–melatonin combination, whereas PRA was down-regulated in the uterus and oviduct after ethanol consumption. MT1R was increased in ovaries and uteri of melatonin-treated rats. Ethanol and melatonin exert opposite effects on E2 and P4, and they differentially regulate the expression of sex steroid receptors in female reproductive tissues.