Shahnaz Babaei Abraki - Shefa Neuroscience Research Center, Khatam-al-Anbia Hospital, Tehran, Iran
Sara Chavoshi- Nezhad - Departments of Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
Mohammad Saied Salehi - Faculty of Biological Sciences, Shahid Beheshti University, Tehran, Iran

Background: GnRH synthesis and its secretion is regulated by vast neural network in hypothalamus. Kisspeptin neurons play important role in regulation of GnRH gene expression and its secretion. Prominent regions of Kisspeptin neurons in the brain are the arcuate nucleus (Arc) and anteroventral periventricular nucleus (AVPV). Kisspeptin binds to GPR54 receptor on membrane of GnRH neuron. GPR54 activates phospholipase C via G proteins, whose activation leads to cleave PI(4,5) P2 into DAG and IP3. Then, IP3 evokes the mobilization of Ca2+ from intracellular stores that leads to secrete GnRH. On the other hand, Kisspeptin activates otx2, transcription factor.Methods: Activated otx2 increases GnRH gene expression via binding to kisspeptin- response element (KsRE) on GnRH promotor. KISS1 system is sensitive to changes in the body energy status.Result: Decrease of Kiss expression and its receptor lead to induction of central Hypogonadism in metabolic disease such as diabetes and obesity.Conclusion: According to important Kiss system in metabolic regulation of reproduction targeting of this signaling can be useful in infertility treating of metabolic disease.

Hypogonadism, IP3, KISS1/GPR54, Metabolic stress, GnRH