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

A, Seiva, Fávaro Wagner, Teixeira, Amorim, Mendes, Fioruci, Pinheiro, Fernandes, Franci, Delella, Martinez Marcelo, Martinez

Description

Melatonin 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. Methods Twenty-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. Results Melatonin 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. Conclusions We 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.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 6
• Langue: English

Extrait

A Chuffaet al.Reproductive Biology and Endocrinology2011,9:108 http://www.rbej.com/content/9/1/108

R E S E A R C HOpen Access Melatonin reduces LH, 17 betaestradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation 1,2 32 21,2 Luiz Gustavo A Chuffa, Fábio RF Seiva , Wagner José Fávaro , Giovana R Teixeira , João PA Amorim, 1,2 1,22 3 Leonardo O Mendes , Beatriz A Fioruci, Patrícia Fernanda F Pinheiro , Ana Angélica H Fernandes , 5 14 2* Janete AA Franci , Flávia K Delella , Marcelo Martinezand Francisco E Martinez

Abstract Background:Melatonin 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. Methods:Twenty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 [100μg/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a.m. Results:Melatonin 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. Conclusions:We 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.

Background Melatonin (Nacetyl5methoxytryptamine) also known as“chemical expression of darkness”is an indolamine produced by pineal gland and secreted in a circadian manner during the night [1]. It is indisputable that mel atonin has been potentially implicated as a therapeutic agent in several conditions. In mammals, melatonin can affect the reproductive function through activation of

* Correspondence: [e-mail] 2 Department of Anatomy, Bioscience Institute, UNESP  Univ. Estadual Paulista, BotucatuSP 18618000, Brazil Full list of author information is available at the end of the article

receptor sites within the hypothalamicpituitarygonadal axis [2]. Previous evidence has suggested that changes consistent with inhibition of GnRH release occur after melatonin implants [3]. Melatonin is found inside ovar ian follicles [4], thus proving its direct action in ovarian function. It has also been proposed that preovulatory follicles contain high amount of melatonin which were indirectly linked to the 17bestradiol (E2) and proges terone (P4) synthesis [5]. In melatonindeprived rats, an increased estrous frequency was inversely related to the luteinizing hormone (LH) and folliclestimulating hor mone (FSH) levels [6]. According to Soares et al. [7],

© 2011 A Chuffa et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.