배경: 성선자극호르몬 유리호르몬(GnRH) 신경세포는 생식기능 조절의 핵심 중추이며, 소마토스타틴(SST)은 뇌하수체 수준에서 reproductive axis를 조절하는 것으로 알려져 있다. 본 연구를 통해 미성숙 마우스 GnRH 신경세포에서 SST의 반응양상 및 성별에 따른 반응성의 차이를 비교하였다. 방법: 미성숙 GnRH 신경세포에서 gramicidin perforated-patch clamp 방법을 이용하여 SST의 반응성을 조사하고, single cell RTPCR 방법을 통한 SSTR2 mRNA 발현 양상의 조사 및 효능제를 이용하여 그 기능적 발현을 조사하였다. 결과: 기록된 미성숙 GnRH 신경세포에서 SST는 주로 세포막 과분극을 유발하였고, 과분극 반응의 경우 농도의존적인 반응을 보였다. SST에 의한 반응양상에서 성별에 대한 차이는 관찰되지 않았다. SST는 흥분성 미성숙 GnRH 신경세포에서 SSTR2 mRNA가 발현되었으며, 효능제인 seglitide에 의해 SST와 유사한 과분극이 관찰되었다. 결론: 본 연구결과는 외인성 SST가 SSTR2를 매개로 시사하부 미성숙 GnRH 신경세포활성을 억제하나 성별에 따른 차이는 없음을 시사하고 있다.

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.