- Somatostatin Inhibits Gonadotropin Releasing Hormone Neuronal Activities in Juvenile Mice.
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Seon Ah Park, Janardhan P Bhattarai, Seong Kyu Han
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Endocrinol Metab. 2011;26(3):210-217. Published online September 1, 2011
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DOI: https://doi.org/10.3803/EnM.2011.26.3.210
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- 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.
- Age-dependent Kisspeptin Effects on the GnRH Neurons in Male and Female Mice.
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Janardhan P Bhattarai, Seon Ah Park, Hua Yin, Soo Joung Park, Jae Gyu Jeon, Kee Wan Chang, So Young Lee, Pan Dong Ryu, Seong Kyu Han
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J Korean Endocr Soc. 2008;23(5):302-309. Published online October 1, 2008
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DOI: https://doi.org/10.3803/jkes.2008.23.5.302
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Abstract
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- BACKGROUND
The gonadotropin releasing hormone (GnRH) neurons play a pivotal role in the central regulation of fertility. Kisspeptin binds to the G-protein coupled receptor 54 (GPR54) and GPR54 has been shown to be essential for puberty and subsequent fertility in humans. The recent in vivo studies have proved that kisspeptin is an extremely potent activator of GnRH neurons. However, the precise mechanism of action of kisspeptin on the GnRH neurons and the age-dependent kisspeptin effects are not yet fully understood. In this study, we investigated the effects of kisspeptin on the GnRH neurons over the developmental stages in male and female mice. METHODS: Young (< P30) and adult (> P35) GnRH-GFP transgenic mice expressing green fluorescent protein were used in this study. Acute coronal brain slices containing the preoptic area were prepared, and the identified GnRH neurons were recorded using the gramicidin perforated-patch clamp technique. RESULTS: In young mice, GnRH neurons were excited by bath application of kisspeptin in 36% (13/36) in male, 17% (4/23) in female tested neurons. In adult mice, GnRH neurons were excited in the majority (30/40, 75%) in male, (21/31, 68%) in female neurons tested. However, there was no significant difference between the effects of kisspeptin in male and female mice. In addition, we tested kisspeptin effects in diestrus, proestrus and estrus animals. There were no significant differences of kisspeptin effects over the estrous cycle. Kisspeptin failed to induce excitatory effects on GnRH neurons (6/7, 86%) neurons) by pretreatment of U73122, a protein lipase C (PLC) inhibitor and kisspeptin-induced excitatory effects were decreased by U73122 application (n = 2). CONCLUSION: These results demonstrated that kisspeptin-induced membrane excitability was increased after puberty and this supports a previous suggestion that GPR54 is essential for puberty and subsequent fertility.
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Citations
Citations to this article as recorded by  - Serum Kisspeptin Levels in Korean Girls with Central Precocious Puberty
Young Jun Rhie, Kee Hyoung Lee, So Hee Eun, Byung Min Choi, Hyun Wook Chae, Ah Reum Kwon, Woo Jung Lee, Jung Hyun Kim, Ho-Seong Kim
Journal of Korean Medical Science.2011; 26(7): 927. CrossRef
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