Meeting Abstract

2.6  Jan. 4  Somatostatin Inhibits Hepatic Growth Hormone Sensitivity by Activating the MAPK Signaling Pathway HAGEMEISTER, A.L.*; SHERIDAN, M.A.; North Dakota State Univ., Fargo Alison.Hagemeister@ndsu.edu

Previously, we reported that somatostatins (SS) inhibit organismal growth by reducing hepatic growth hormone (GH) sensitivity and by inhibiting insulin-like growth factor-1 (IGF-I) production. In this study, we used hepatocytes isolated from rainbow trout to elucidate the mechanism(s) associated with the growth-inhibiting actions of SS. SS-14, a predominant SS isoform, stimulated tyrosine phosphorylation of several endogenous proteins, including mitogen-activated protein kinase (MAPK). SS-14 specifically activated phospho-MAPK in a dose-dependant fashion. This activation occurred within 5 minutes and disappeared after 1 hour. The MAPK inhibitor U0126 retarded SS-14-stimulated phosphorylation of MAPK. U0126 also blocked SS-inhibition of GH receptor (GHR) and IGF-I mRNA expression. SS-14 also activated MAPK in Chinese hamster ovarian cells transfected with trout SS receptor (SSTR) subtype 1A and 1B in a dose- and time-dependant manner. These results suggest that SS inhibits hepatic GHR and IGF-I expression by activating the MAPK pathway. Moreover, the activation of the MAPK pathway appears linked to the SSTR subtype 1 receptor. (Supported by NSF IOB 0444860.)