Melatonin Receptor Activation Regulates GnRH Gene Expression and Secretion in GT1–7 GnRH Neurons

Abstract

Melatonin plays a significant role in the control of the hypothalamic-pituitary-gonadal axis. Using the GT1-7 cell line, an in vitro model of GnRH-secreting neurons of the hypothalamus, we examined the potential signal transduction pathways activated by melatonin directly at the level of the GT1-7 neuron. We found that melatonin inhibits forskolin-stimulated adenosine 3-, 5-cyclic monophosphate accumulation in GT1-7 cells through an inhibitory G protein. Melatonin induced protein kinase C activity by 1.65-fold over basal levels, increased the phosphorylation of extracellular signal-regulated kinase 1 and 2 proteins, and activated c-fos and junB mRNA expression in GT1-7 cells. Using the protein kinase A inhibitor H-89, the protein kinase C inhibitor bisindolylmaleimide, and the mitogen-activated protein kinase kinase inhibitor PD98059, we found that the melatonin-mediated cyclical regulation of GnRH mRNA expression may involve the protein kinase C and the extracellular signal-regulated kinase 1 and 2 pathways, but not the protein kinase A pathway. We found that melatonin suppresses GnRH secretion by ϳ45% in the GT1-7 neurons. However, in the presence of the inhibitors H-89, bisindolylmaleimide, and PD98059 melatonin was unable to suppress GnRH secretion. These results provide insights into the potential signal transduction mechanisms involved in the control of GnRH gene expression and secretion by melatonin.

Melatonin Attenuates the Cerebral Ischemic Injury via the MEK/ERK/p90RSK/Bad Signaling Cascade

“…Previous studies have shown that ERK1/2 is activated by phosphorylation in response to melatonin, leading to attenuation of neuronal cell damage by ischemic injury [7]. Also, melatonin increases ERK1/2 phosphorylation levels in neuronal cell cultures [18]. This study demonstrated that the levels of ERK1/2 up-stream enzymes, phospho-Raf-1 and phospho-MEK1/2, decrease in cases of brain injury, and melatonin prevented the dephos- phorylation of these kinases.…”

Night shift work and other determinants of estradiol, testosterone, and dehydroepiandrosterone sulfate among middle-aged nurses and midwives

“…Night work and artificial light at night may affect human physiology, introducing changes in the regulation of the circadian rhythm, with a reduction of melatonin synthesis and changes in the profiles of other hormones. Some speculations point to an interrelation between melatonin and E2, which results in decreased melatonin synthesis leading to an increase in E2 concentration (40)(41)(42). It has been hypothesized that women working night shifts for many years may have up-regulated hypothalamic gonadal axis (with increase of circulating estrogenes) as a result of decreased melatonin (43).…”

Physiological adaptations of small mammals to desert ecosystems

“…The pulsatile secretion of gonadotropin-releasing hormone (GnRH), from a small number of neurons in the hypothalamus, controls luteinizing hormone and follicle-stimulating hormone secretion, which, in turn, regulates the functional activity of gonads (Glass & Knotts 1987;Kennaway & Rowe 1995). Melatonin has been shown to downregulate GnRH gene expression in a cyclical pattern over a 24-h period (Roy & Belsham 2002).…”