Somatostatin actions on a protein kinase C-dependent growth hormone secretagogue cascade.
In mammals, the ability of somatostatin (SS) to block growth hormone (GH) secretion is due, in part, to the inhibition of two key intracellular mediators, cAMP and Ca2+. We examined whether or not inhibition of Ca2+ signaling was mediating SS-induced inhibition basal, as well as gonadotropin-releasing hormone (GnRH; a protein kinase C (PKC)-dependent growth hormone secretagogue)-stimulated growth hormone (GH) release. Although SS reduced basal GH release from populations of pituitary cells, parallel reductions in [Ca2+]i were not observed within single, identified somatotropes. Similarly, application of GnRH and the PKC activator DiC8 elicited increases in [Ca2+]i and GH release, but abolition of the Ca2+ responses did not accompany SS inhibition of the GH responses. Surprisingly, while DiC8 potentiated SS inhibition of GH release, SS paradoxically increased DiC8-stimulated increases in [Ca2+]i. These data establish that abolition of Ca2+ signals is not a primary mechanism through which SS lowers basal, or inhibits GnRH-stimulated hormone release.
Yunker
W K
WK
Department of Biological Sciences, CW 405 Biological Sciences Building, Faculty of Science, University of Alberta, Edmonton, T6G 2E9, Alberta, Canada.
Chang
J P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D018929:Cell Culture Techniques; D004075:Diglycerides / Q000494:pharmacology; D006054:Goldfish; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects*; D013006:Growth Hormone / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008322:Mammals; D010902:Pituitary Gland / Q000166:cytology; D011493:Protein Kinase C / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*
D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; D013006:Growth Hormone; D011493:Protein Kinase C; D002118:Calcium