Evaluation of melatonin on the precocious puberty: a pilot study

Holanda, Felisbela Soares de; Tufik, Sérgio; Bignotto, Magda; Maganhin, Carla G.; Vieira, Lúcia Helena Laprano; Baracat, Edmund Chada; Soares, José Maria

doi:10.3109/09513590.2010.501888

Cited by 20 publications

(16 citation statements)

References 27 publications

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“…Melatonin plays a pivotal role in female reproduction, including puberty, ovarian follicle growth, ovulation, and luteinization [ 29 , 30 , 31 ]. Several studies have demonstrated that melatonin has beneficial effects on oocyte maturation and subsequent embryo development in many species, such as mice [ 32 ], cattle [ 33 ], and pigs [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Promotes Ubiquitination of Phosphorylated Pro-Apoptotic Protein Bcl-2-Interacting Mediator of Cell Death-Extra Long (BimEL) in Porcine Granulosa Cells

Wang

Zeng

2018

IJMS

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Melatonin (N-acetyl-5-methoxytryptamine) is found in ovarian follicular fluid, and its concentration is closely related to follicular health status. Nevertheless, the molecular mechanisms underlying melatonin function in follicles are uncertain. In this study, melatonin concentration was measured in porcine follicular fluid at different stages of health. The melatonin concentration decreased as the follicles underwent atresia, suggesting that melatonin may participate in the maintenance of follicular health. The molecular pathway through which melatonin may regulate follicular development was further investigated. The pro-apoptotic protein BimEL (Bcl-2-interacting mediator of cell death-Extra Long), a key protein controlling granulosa cell apoptosis during follicular atresia, was selected as the target molecule. BimEL was downregulated when porcine granulosa cells were cultured in medium containing 10−9 M melatonin and isolated cumulus oocyte complexes (COCs) or follicle stimulating hormone (FSH). Interestingly, ERK-mediated phosphorylation was a prerequisite for the melatonin-induced decline in BimEL, and melatonin only promoted the ubiquitination of phosphorylated BimEL, and did not affect the activities of the lysosome or the proteasome. Moreover, the melatonin-induced downregulation of BimEL was independent of its receptor and its antioxidant properties. In conclusion, melatonin may maintain follicular health by inducing BimEL ubiquitination to inhibit the apoptosis of granulosa cells.

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Section: Discussionmentioning

confidence: 99%

Melatonin Promotes Ubiquitination of Phosphorylated Pro-Apoptotic Protein Bcl-2-Interacting Mediator of Cell Death-Extra Long (BimEL) in Porcine Granulosa Cells

Wang

Zeng

2018

IJMS

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“…Interestingly, melatonin secretion has been associated with reproductive development and the timing of human puberty in some studies [14]–[16]. However aspects of this work has methodological flaws [14], [15] and other studies have failed to replicate the finding [17], [18].…”

Section: Introductionmentioning

confidence: 90%

Regulation of Pituitary MT1 Melatonin Receptor Expression by Gonadotrophin-Releasing Hormone (GnRH) and Early Growth Response Factor-1 (Egr-1): In Vivo and In Vitro Studies

et al. 2014

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Melatonin receptor expression exhibits profound developmental changes through poorly understood mechanisms. In mammals, a current model suggests that pubertal reactivation of gonadotrophin-releasing hormone (GnRH) secretion down-regulates MT1 melatonin receptors in pituitary gonadotroph cells, via the induction of early growth response factor-1 (EGR-1). Here we have examined this model by testing the hypotheses that inhibition of Mt1 expression by GnRH occurs directly in gonadotroph cells, can be reversed in adulthood by blockade of GnRH receptors, and requires EGR-1. We first confirmed the endogenous expression of Mt1 mRNA in the αT3-1 gonadotroph cell line. Stimulation of these cells with a GnRH agonist resulted in a rapid increase of Egr-1 mRNA expression, which peaked after 30–60 minutes, and a more prolonged elevation of nuclear EGR-1 immunoreactivity. Moreover, the GnRH agonist significantly decreased Mt1 mRNA. We then treated adult male rats with the GnRH antagonist cetrorelix or saline. After 4 weeks of daily injections, cetrorelix significantly reduced serum LH concentration and testis weight, with histological analysis confirming absence of spermatogenesis. Despite the successful inhibition of GnRH signalling, pituitary Mt1 expression was unchanged. Next we studied the proximal region of the rat Mt1 promoter. Consistent with previous work, over-expression of the transcription factor PITX-1 increased Mt1-luciferase reporter activity; this effect was dependent on the presence of consensus PITX-1 promoter binding regions. Over-expression of EGR-1 inhibited PITX-1-stimulated activity, even following mutation of the consensus EGR-1 binding site. Finally, we studied Egr1 −/− mice and observed no difference in pituitary Mt1 expression between Egr1 −/− and wild-type litter mates. This work demonstrates that GnRH receptor activation directly down-regulates Mt1 expression in gonadotroph cells. However, pituitary Mt1 expression in adults is unaltered by blockade of GnRH signalling or absence of EGR-1. Our data therefore suggest that melatonin receptor regulation by GnRH is not reversible in adulthood and doesn't require EGR-1.

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“…A number of animal studies (Arendt, ; Hoffman & Reiter, ; Srinivasan et al, ) have suggested that elevated melatonin levels during the prepubertal periods helps to maintain the hypothalamic–pituitary–gonadal axis in a state of quiescence, thus inhibiting the onset of pubertal development; while the reduction in melatonin levels that begin at the onset of puberty activates hypothalamic pulsatile secretion of gonadotropin‐releasing hormone resulting in the onset of puberty (Murcia García et al, ). In a few human studies, there have been reports that have associated precocious puberty with low melatonin levels (Commentz & Helmke, ; de Holanda et al, ), although clinical studies have yielded inconclusive and/or conflicting results (Srinivasan et al, ).…”

Section: Exogenous Melatonin Use and Sexual Maturation In Adolescentsmentioning

confidence: 99%

Melatonin, adolescence, and the brain: An insight into the period‐specific influences of a multifunctional signaling molecule

Onaolapo

2017

Birth Defects Research

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Melatonin is a neurohormone that is involved in the modulation of a wide range of physiological processes, including maintenance of the circadian rhythm, mediation of photoperiodic information, regulation of the sleep-wake cycle, synchronization of cell physiology, antioxidant defense, and immune-modulation. Although there are reports of increasing use of melatonin in the management of a number of health conditions, evidence exists that is suggestive of deleterious effects of melatonin administration on brain and reproductive development in the prepubertal and pubertal periods that are within the teenage years. In this review, we examine the influences of endogenous and exogenous melatonin on the adolescent brain, with specific reference to its involvement in the evolution of brain functions, brain structure, sleep regulation, and modulation of behaviors in health or disease.

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Evaluation of melatonin on the precocious puberty: a pilot study

Abstract: Despite the sleep data, melatonin may be involved in the precocious puberty process.

Cited by 20 publications

References 27 publications

Melatonin Promotes Ubiquitination of Phosphorylated Pro-Apoptotic Protein Bcl-2-Interacting Mediator of Cell Death-Extra Long (BimEL) in Porcine Granulosa Cells

Melatonin Promotes Ubiquitination of Phosphorylated Pro-Apoptotic Protein Bcl-2-Interacting Mediator of Cell Death-Extra Long (BimEL) in Porcine Granulosa Cells

Regulation of Pituitary MT1 Melatonin Receptor Expression by Gonadotrophin-Releasing Hormone (GnRH) and Early Growth Response Factor-1 (Egr-1): In Vivo and In Vitro Studies

Melatonin, adolescence, and the brain: An insight into the period‐specific influences of a multifunctional signaling molecule

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