NeuroendocrinologySuppression of GnRH gene expression in GT1-1 hypothalamic neuronal cells: action of protein kinase CSun, Woong1; Choe, Young S.1; Lee, Young J.2; Kim, Kyungjin1,3Author Information 1Department of Molecular Biology and Research Center for Cell Differentiation, College of Natural Sciences, Seoul National University, Seoul 151–742, Korea 2Department of Radiation Oncology Research Laboratory, William Beaumont Hospital, 3601 West Thirteen Mile Road, Royal Oak, Michigan 48073-6769, USA 3Corresponding Author: Kyungjin Kim Received 24 July 1997; accepted 21 August 1997 NeuroReport: November 10th, 1997 - Volume 8 - Issue 16 - p 3541-3545 Buy Abstract WE attempted to elucidate molecular mechanisms of gonadotropin-releasing hormone (GnRH) gene regulation by the protein kinase C (PKC) pathway in GT1-1 cells. Activation of PKC with 12-tetra-decanoylphorbol13-acetate (TPA) or inhibition with staurosporine or calphostin C down-regulated GnRH mRNA levels. A serial deletion mutant analysis revealed that this suppression was mediated by the proximal region (−187/−69) of the mouse GnRH promoter. TPA transiently induced c-fos mRNA, whereas staurosporine or calphostin C failed to do so. However, PKC inhibitors blocked the TPA-evoked c-fos induction. Over-expression of PKCα down-regulated GnRH promoter activity, indicating that PKC activation was sufficient to inhibit GnRH gene expression. These results suggest that both activation and inhibition of PKC decrease the GnRH gene expression in the GT1-1 cells probably through different signal cascade mechanisms. © Lippincott-Raven Publishers.