Sexually Dimorphic Modulation of GABAA Receptor Currents by Melatonin in Rat Gonadotropin-Releasing Hormone Neurons

Abstract

Gonadotropin-releasing hormone (GnRH) neurons represent the final output neurons in the central control of reproduction. γ-Amino butyric acid (GABA), one of the major regulators of GnRH neurons, depolarizes GnRH neurons isolated from adult rats via GABA A receptors. The presence of GABA A receptors in GnRH neurons has also been demonstrated morphologically. Furthermore, the pineal hormone melatonin is involved in the regulation of reproductive function, including the timing of the luteinizing hormone surge. The suprachiasmatic nucleus and the GABAergic system in the medial preoptic area are considered as possible sites of the action of melatonin. Until now, however, a direct action of melatonin on GnRH neurons has not been reported. Therefore we examined the effect of melatonin on GABA A receptor currents in GnRH neurons isolated from GnRH-EGFP transgenic rats by means of perforated patchclamp experiments. The GABA A receptor currents were modulated by melatonin in a sex-specific manner. In GnRH neurons from adult males, melatonin augmented these currents in 67% of the neurons examined, but attenuated the currents in only 19% of them. These modulations were blocked by the melatonin receptor antagonist luzindole, suggesting an involvement of melatonin receptors. The modulation by melatonin was not observed in GnRH neurons isolated from infantile rats. These findings indicate that GABA affects the excitability of GnRH neurons in adult rats through GABA A receptors, and that melatonin modifies this excitability via melatonin receptors in a sex-specific manner.

Cetrorelix, a Gonadotropin-Releasing Hormone Antagonist, Induces the Expression of Melatonin Receptor 1a in the Gonadotropin-Releasing Hormone Neuronal Cell Line GT1–7

“…These electrophysiological results clearly indicated the expression of functional MT1 as previously demonstrated by coexpression of MT1 and GABA A R in HEK293 cells [32], although the melatonin concentration is pharmacological. In our recent study [20], a significant modulation of the GABA A R currents was observed with 10 n M or higher concentrations of melatonin in endogenous GnRH neurons. Melatonin, however, tended to attenuate the currents in GT1–7 cells treated with vehicle alone.…”

“…We previously developed transgenic rats that express enhanced green fluorescent protein specifically in GnRH neurons under the GnRH promoter [17]. Using these animals, we analyzed several types of electrical activities in endogenous GnRH neurons [17,18,19,20,21]. We recently showed that melatonin modulates type-A γ-aminobutyric acid (GABA) receptor (GABA A R) currents in adult rat GnRH neurons in a sexually dimorphic manner [20].…”

“…Using these animals, we analyzed several types of electrical activities in endogenous GnRH neurons [17,18,19,20,21]. We recently showed that melatonin modulates type-A γ-aminobutyric acid (GABA) receptor (GABA A R) currents in adult rat GnRH neurons in a sexually dimorphic manner [20]. Melatonin augments the currents in male GnRH neurons, while it reduces the currents in female neurons, suggesting a differential expression of MT1 and MT2 in male and female rats to elicit the dimorphic response.…”

Gene structures, biochemical characterization and distribution of rat melatonin receptors

“…However, direct regulatory actions of melatonin on GnRH neurons are still unknown. Our previous study showed that melatonin directly modulates GABA A receptor currents in adult rat GnRH neurons in a sexually dimorphic manner [28]. In male GnRH neurons, melatonin augments the currents, suggesting a preferential expression of MT1, because MT1 and MT2 differentially modulate GABA A receptor functions [29].…”

An Overview On Melatonin Hormone

“…GABA, GABA reseptör aracılığıyla GnRH nöronlarının uyarıla-bilirliğini etkilemekte ve melatoninin ise melatonin reseptör aracılığıyla bu uyarılabilirliği değiştirebilmektedir. [47] Ayrıca melatonin hormonunun LH dalgalanmasını içeren üreme işlevlerini düzenlenmesinde rol oynadığı bildirilmiştir. Valcavi ve arkadaşlarının yaptığı bir çalışmada melatoninin hormonunun büyüme hormonu (GH) salınımını GnRH'dan daha hızlı uyardığı bulunmuştur.…”