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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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 [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.

Related collections

Most cited references 54

Record: found
Abstract: found
Article: not found

Cloning of a novel receptor expressed in rat prostate and ovary.

G G Kuiper, E Enmark, M Pelto-Huikko … (1996)

We have cloned a novel member of the nuclear receptor superfamily. The cDNA of clone 29 was isolated from a rat prostate cDNA library and it encodes a protein of 485 amino acid residues with a calculated molecular weight of 54.2 kDa. Clone 29 protein is unique in that it is highly homologous to the rat estrogen receptor (ER) protein, particularly in the DNA-binding domain (95%) and in the C-terminal ligand-binding domain (55%). Expression of clone 29 in rat tissues was investigated by in situ hybridization and prominent expression was found in prostate and ovary. In the prostate clone 29 is expressed in the epithelial cells of the secretory alveoli, whereas in the ovary the granuloma cells in primary, secondary, and mature follicles showed expression of clone 29. Saturation ligand-binding analysis of in vitro synthesized clone 29 protein revealed a single binding component for 17beta-estradiol (E2) with high affinity (Kd= 0.6 nM). In ligand-competition experiments the binding affinity decreased in the order E2 > diethylstilbestrol > estriol > estrone > 5alpha-androstane-3beta,17beta-diol > testosterone = progesterone = corticosterone = 5alpha-androstane-3alpha,17beta-diol. In cotransfection experiments of Chinese hamster ovary cells with a clone 29 expression vector and an estrogen-regulated reporter gene, maximal stimulation (about 3-fold) of reporter gene activity was found during incubation with 10 nM of E2. Neither progesterone, testosterone, dexamethasone, thyroid hormone, all-trans-retinoic acid, nor 5alpha-androstane-3alpha,I7beta-diol could stimulate reporter gene activity, whereas estrone and 5alpha-androstane-3beta,17beta-diol did. We conclude that clone 29 cDNA encodes a novel rat ER, which we suggest be named rat ERbeta to distinguish it from the previously cloned ER (ERalpha) from rat uterus.

0 comments Cited 181 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Human pineal physiology and functional significance of melatonin.

M Macchi, Jeffrey N. Bruce (2015)

Descriptions of the pineal gland date back to antiquity, but its functions in humans are still poorly understood. In both diurnal and nocturnal vertebrates, its main product, the hormone melatonin, is synthesized and released in rhythmic fashion, during the dark portion of the day-night cycle. Melatonin production is controlled by an endogenous circadian timing system and is also suppressed by light. In lower vertebrates, the pineal gland is photosensitive, and is the site of a self-sustaining circadian clock. In mammals, including humans, the gland has lost direct photosensitivity, but responds to light via a multisynaptic pathway that includes a subset of retinal ganglion cells containing the newly discovered photopigment, melanopsin. The mammalian pineal also shows circadian oscillations, but these damp out within a few days in the absence of input from the primary circadian pacemaker in the suprachiasmatic nuclei (SCN). The duration of the nocturnal melatonin secretory episode increases with nighttime duration, thereby providing an internal calendar that regulates seasonal cycles in reproduction and other functions in photoperiodic species. Although humans are not considered photoperiodic, the occurrence of seasonal affective disorder (SAD) and its successful treatment with light suggest that they have retained some photoperiodic responsiveness. In humans, exogenous melatonin has a soporific effect, but only when administered during the day or early evening, when endogenous levels are low. Some types of primary insomnia have been attributed to diminished melatonin production, particularly in the elderly, but evidence of a causal link is still inconclusive. Melatonin administration also has mild hypothermic and hypotensive effects. A role for the pineal in human reproduction was initially hypothesized on the basis of clinical observations on the effects of pineal tumors on sexual development. More recent data showing an association between endogenous melatonin levels and the onset of puberty, as well as observations of elevated melatonin levels in both men and women with hypogonadism and/or infertility are consistent with such a hypothesis, but a regulatory role of melatonin has yet to be established conclusively. A rapidly expanding literature attests to the involvement of melatonin in immune function, with high levels promoting and low levels suppressing a number of immune system parameters. The detection of melatonin receptors in various lymphoid organs and in lymphocytes suggests multiple mechanisms of action. Melatonin has been shown to be a powerful antioxidant, and has oncostatic properties as well, both direct and indirect, the latter mediated by its effects on reproductive hormones. Finally, there are reports of abnormal daily melatonin profiles in a number of psychiatric and neurological disorders, but the significance of such abnormalities is far from clear.

0 comments Cited 106 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform.

F DeMayo, John P. Lydon, Orla Conneely … (2003)

Progesterone (P) regulates female reproduction via two nuclear receptors, PR-A and PR-B. Although both receptors display overlapping and distinct transcription regulatory properties, their individual physiological roles are unclear. To address the physiological role of PR-A, we generated a mouse model in which expression of PR-B was specifically ablated (PRBKO-/-). We show that selective activation of PR-A in PRBKO-/- mice is sufficient to elicit normal ovarian and uterine responses to P but results in reduced mammary gland morphogenesis. In the absence of PR-B, pregnancy-associated ductal sidebranching and lobuloalveolar development are markedly reduced due to decreased ductal and alveolar epithelial cell proliferation and decreased survival of alveolar epithelium. In an effort to elucidate the molecular genetic signaling pathways that are differentially regulated by PRs in the mammary gland, we have identified receptor activator of nuclear factor kappa B ligand (RANKL) as a paracrine mediator of P-dependent alveologenesis. Further, we demonstrate that the defects in PRBKO-/- mice are associated with an inability of PR-A to activate the RANKL signaling pathway in response to P. Our data indicate that functional interaction between PR-A and PR-B is not required for reproductive activity and that selective modulation of PR-A activity by progestin agonists may have a protective effect against both uterine and mammary gland hyperplasias.

0 comments Cited 95 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Reprod Biol Endocrinol

Title: Reproductive Biology and Endocrinology : RB&E

Publisher: BioMed Central

ISSN (Electronic): 1477-7827

Publication date Collection: 2011

Publication date (Electronic): 2 August 2011

Volume: 9

Page: 108

Affiliations

[1 ]Department of Structural and Cellular Biology, Institute of Biology, Universidade Estadual de Campinas - UNICAMP, Campinas-SP 13083-863, Brazil

[2 ]Department of Anatomy, Bioscience Institute, UNESP - Univ. Estadual Paulista, Botucatu-SP 18618-000, Brazil

[3 ]Department of Chemistry and Biochemistry, Bioscience Institute, UNESP - Univ. Estadual Paulista, Botucatu-SP 18618-000, Brazil

[4 ]Department of Morphology and Pathology, UFSCar - Universidade Federal de São Carlos, São Carlos-SP 13565-905, Brazil

[5 ]Department of Morphology, Stomatology and Physiology, USP - Universidade de São Paulo, Ribeirão Preto-SP 14040-900, Brazil

Article

Publisher ID: 1477-7827-9-108

DOI: 10.1186/1477-7827-9-108

PMC ID: 3161940

PubMed ID: 21810236

SO-VID: 1984f6cd-4352-4a79-aac1-dc3280314726

License:

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.

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

Read this article at

Abstract

Background

Methods

Results

Conclusions

Related collections

Genome Engineering using CRISPR

Most cited references 54

Cloning of a novel receptor expressed in rat prostate and ovary.

Human pineal physiology and functional significance of melatonin.

Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform.

Author and article information

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 66

Cited by 24

Most referenced authors 446