Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation

Abstract

BackgroundMelatonin is associated with direct or indirect actions upon female reproductive function. However, its effects on sex hormones and steroid receptors during ovulation are not clearly defined. This study aimed to verify whether exposure to long-term melatonin is able to cause reproductive hormonal disturbances as well as their role on sex steroid receptors in the rat ovary, oviduct and uterus during ovulation.MethodsTwenty-four adult Wistar rats, 60 days old (+/- 250 g) were randomly divided into two groups. Control group (Co): received 0.9% NaCl 0.3 mL + 95% ethanol 0.04 mL as vehicle; Melatonin-treated group (MEL): received vehicle + melatonin [100 μg/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a.m.ResultsMelatonin significantly reduced the plasma levels of LH and 17 beta-estradiol, while urinary 6-sulfatoximelatonin (STM) was increased at the morning estrus. In addition, melatonin promoted differential regulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and melatonin receptor (MTR) along the reproductive tissues. In ovary, melatonin induced a down-regulation of ER-alpha and PRB levels. Conversely, it was observed that PRA and MT1R were up-regulated. In oviduct, AR and ER-alpha levels were down-regulated, in contrast to high expression of both PRA and PRB. Finally, the ER-beta and PRB levels were down-regulated in uterus tissue and only MT1R was up-regulated.ConclusionsWe suggest that melatonin partially suppress the hypothalamus-pituitary-ovarian axis, in addition, it induces differential regulation of sex steroid receptors in the ovary, oviduct and uterus during ovulation.

Effect of exogenous melatonin on embryo viability and uterine environment in undernourished ewes

“…The mechanisms by which melatonin may influence the expression of the uterine steroid receptors are not easy to understand since no references about a direct action of melatonin at the uterine level through specific receptors in the reproductive tract of the sheep have been reported. However, Zhao et al (2002) characterized the melatonin receptor (MT 1 ) transcript in rat endometrium during oestrous cycle, and more recently, Chuffa et al (2011) described that the expression of MT 1 is up-regulated by the melatonin treatment and is associated with the down-regulation of the ER-beta and PRB in the reproductive tissue of rats.…”

Characterization of Chemically Induced Ovarian Carcinomas in an Ethanol-Preferring Rat Model: Influence of Long-Term Melatonin Treatment

“…Under normal conditions, melatonin at doses of 200 µg/100 g of BW/day induced longer estrous periods and reductions in ovarian weight [43]. Our previous reports suggested that long-term mel treatment satisfactorily reduces ovarian lipoperoxidation and plasma estradiol levels, while enhancing tissue antioxidant defenses [27], [28]. Moreover, mel treatment was also associated with lower ovarian weights and estrous cycle synchronization [44].…”

Melatonin membrane receptors in peripheral tissues: Distribution and functions

“…The expression of these receptors is up-regulated by the melatonin treatment and is associated with the down-regulation of the ER-beta and PRB (Chuffa et al, 2011). Influence of the melatonin on the incidence of endometrial cancer has been suggested (Sandyk et al, 1992) and the presence of the functional MT2 receptor was detected in the estrogen positive cell line derived from patient with endometrial carcinoma (Kobayashi et al, 2003).…”