ArticlePloS one2014
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.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Melatonin receptor signaling in human pathologies: from molecular mechanisms to therapeutic targets.Function (Oxford, England) · 2026Review
- Circadian rhythm of melatonin receptors under monochromatic light and their regulatory effect on clock genes in the chick liver.Poultry science · 2026Article
- Novel Insights into the Distribution and Effects of Perfluorooctanesulfonic acid (PFOS) in the Nervous System of a Frog Tadpole Model by Mass Spectrometry Imaging.Environmental science & technology · 2026Article
- Precocious puberty under stressful conditions: new understanding and insights from the lessons learnt from international adoptions and the COVID-19 pandemic.Frontiers in endocrinology · 2023Review
- Analysis of the Incidence and Risk Factors of Precocious Puberty in Girls during the COVID-19 Pandemic.International journal of endocrinology · 2022Article
- Effects of Melatonin on Anterior Pituitary Plasticity: A Comparison Between Mammals and Teleosts.Frontiers in endocrinology · 2020Review
- Melatonin mediates seasonal transitions in aggressive behavior and circulating androgen profiles in male Siberian hamsters.Hormones and behavior · 2020Article
- Neural Androgen Synthesis and Aggression: Insights From a Seasonally Breeding Rodent.Frontiers in endocrinology · 2018Review
- Endotoxin-Induced Inflammation Suppresses the Effect of Melatonin on the Release of LH from the Ovine Pars Tuberalis Explants-Ex Vivo Study.Molecules (Basel, Switzerland) · 2017Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
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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