Serotonin stimulates GnRH secretion through the c-Src-PLC γ1 pathway in GT1–7 hypothalamic cells

Abstract

Serotonin is a neurotransmitter that alters the hypothalamicpituitary-adrenal axis. To date, however, the molecular mechanisms underlying the role of serotonin in hormone secretion have remained largely unclear. In this study, we report that serotonin activates phospholipase C (PLC) g1 in an Src-dependent manner in hypothalamic GT1-7 cells, and that pretreatment with either 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazole [3, 4-d] pyrimidine, an Src-kinase inhibitor, or U73122, a PLC inhibitor, attenuates the serotonin-induced increase in calcium levels. Also, PLC g1 binds to c-Src through the Src-homology (SH) 223 domain upon serotonin treatment. Moreover, calcium increase is alleviated in the cells transiently expressing SH223 domain-deleted PLC g1 or lipase inactive mutant PLC g1, as compared with cells transfected with wild-type PLC g1. Furthermore, the inhibition of the activities of either PLC or Src results in a significant diminution of the serotonin-induced release of gonadotropin-releasing hormone (GnRH). In addition, the results of our smallinterfering RNA experiment confirm that endogenous PLC g1 is a prerequisite for serotonin-mediated signaling pathways. Taken together, our findings demonstrate that serotonin stimulates the release of GnRH through the Src-PLC g1 pathway, via the modulation of intracellular calcium levels.

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A social and Biological Approach for Postpartum Depression in Egypt

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