Somatostatin Inhibits Gonadotropin Releasing Hormone Neuronal Activities in Juvenile Mice

BACKGROUND: The gonadotropin releasing hormone (GnRH) neurons perform a pivotal function in the central regulation of fertility. Somatostatin (SST) is an important neuromodulatory peptide in the central nervous system and alters neuronal activities via G protein- coupled SST receptors. A number of studies have shown that SST modulates the reproductive axis at the hypothalamic level. However, the precise action mechanisms of SST and related receptor subtypes have yet to be fully understood. In this study, we evaluated the direct effects of SST on GnRH neurons in juvenile mice. METHODS: Juvenile (postnatal days, < PND 30) GnRH-GFP transgenic mice expressing green fluorescent protein were used in this study. Acute coronal brain slices containing the preoptic area were prepared and all identified GnRH neurons were recorded using the gramicidin perforated-patch clamp technique; type II SST receptor (SSTR2) mRNA expression was evaluated via single cell reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: SST caused membrane hyperpolarization, depolarization, no response, or membrane hyperpolarization with a reduction of action potential. Most (57.7%, 30/52) of the GnRH neurons tested were hyperpolarized by SST and this SST-induced hyperpolarization was found to be concentration-dependent. The percentage of responses, membrane potential changes (MPC), and resting membrane potential (RMP) by SST were not significantly different in juvenile male and female GnRH neurons. The SST-induced hyperpolarization was maintained in the presence of tetrodotoxin (TTX), a sodium channel blocker, and an amino acid blocking cocktail (AABC) containing AP-5 (NMDA receptor antagonist), CNQX (non-NMDA glutamate receptor antagonist), picrotoxin (GABAA receptor antagonist), and strychnine (glycine receptor antagonist). SSTR2 mRNA was expressed on 10 (38%) among 26 GnRH neurons. Seglitide, an SSTR2 agonist, mimicked this SST-induced hyperpolarization (11/23 47.8%) and this response was maintained in the presence of TTX and AABC. CONCLUSION: Our data show that SST can exert potent inhibitory action against GnRH neuronal excitability via SSTR2 activation in juvenile mice.

Effects of Dopamine on the Gonadotropin Releasing Hormone(GnRH) Neurons / 대한내분비학회지

BACKGROUND: The gonadotropin releasing hormone (GnRH) neurons represent the final output cells of the neural network that controls fertility. Dopamine (DA) has been shown to control gonadotropin release in many species. However, the direct membrane effects of DA and the related receptors on GnRH neurons remain poorly understood. The purpose of this study was to investigate the direct actions of DA on GnRH neurons and the related receptors using brain slice electrophysiology. METHODS: Gramicidin-perforated patch clamp recordings were made from the GnRH neurons to examine the direct membrane effects of DA in GnRH-EGFP mut5 mice. RESULTS: DA induced hyperpolarization of the GnRH neurons, which was maintained in the presence of tetrodotoxin (TTX), a Na+ channel blocker, suggesting a direct, rather than indirect, action of DA on GnRH neurons. DA-induced hyperpolarizing effects were blocked by prazosin, an alpah1-adrenergic antagonist, and mimicked by phenylephrine (PE), an alpha1-adrenergic agonist. CONCLUSIONS: These data indicate that DA exerts a direct inhibitory effect on GnRH neurons via the alpha1- adrenergic receptors. These results support the general concept that dopaminergic afference represents a predominantly inhibitory component of the GnRH neuronal network.