GHRP-6 Induces CREB Phosphorylation and Growth Hormone Secretion via a Protein Kinase Cσ-dependent Pathway in GH3 Cells

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 30; no. 2; pp. 183 - 187
• Main Author: 田春雷 叶飞 徐同江 王胜 王晓丹 王和平 万锋 雷霆
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01-04-2010; Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
• Subjects: CREB; GHRP; Medicine; Medicine & Public Health; 激素分泌; 生长激素; 磷酸化; 蛋白激酶C; CREB; growth hormone secretagogues; growth hormone; protein kinase C
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-010-0210-5

This study examined the effect of GHRP-6, a known GHSs receptor agonist, on the phosphorylation of cAMP-responsive element-binding protein （CREB） and the tmderly mechanism. GH3 cells were cultured and subjected to different treatments as follows： GHRP-6, GHRP-6 plus GHRH, phorbol ester （PMA）, an activator of PKC, alone or in combination with GHRP-6, G66983, a general inhibitor of PKCs, in the presence or absence of GHRP-6, rottlerin, an inhibitor of PKCs, alone or plus GHRP-6. The cells were transiently transfected with PKCσ-specific siRNA and then treated with GHRP-6. GH level was measured by enzyme-linked immunosorbent assay （ELISA）. The expression of phosphor-CREB, PKCσ, PKC0 and phosphor-PKCo was determined by Western blotting. The results showed that GHRP-6 stimulated GH secretion in both time- and dose-dependent manners and enhanced the effect of GHRH on GH secretion. GHRP-6 was also found to induce CREB phosphorylation. Moreover, GH secretion was enhanced by the PKC activator PMA and reduced by the PKC inhibitors （G66983, rottlerin） and knockdown of PKCσ. PKCσ could be activated by GHRP-6. It is concluded that PKC, especialiy PKCσ, mediates CREB phosphorylation and GHRP-6-induced GH secretion.