Meeting Abstract
P2.43 Friday, Jan. 4 Somatostatin Inhibits the Expression of Insulin-like Growth Factor-I Receptors VERY, N.; POUDYAL, D.; HANSON, A.; SHERIDAN, M.A.*; North Dakota State Univ., Fargo Mark.Sheridan@ndsu.edu
Somatostatins (SSs) inhibit organismal growth by reducing the release of growth hormone (GH) from the pituitary and by reducing the sensitivity to GH and the production of insulin-like growth factor-I (IGF-I) in target tissues. In this study, we used rainbow trout to examine the role of SSs on IGF-I receptor (IGFR1) expression. Trout possess two distinct IGFR1 mRNAs, IGFR1A and IGFR1B, and both are in high abundance in the gill. Implantation of fish with SS-14-I (a highly conserved form of SS) for 20 days significantly reduced IGFR1A and IGFR1B mRNA levels and lowered microsomal 125I-IGF-I binding in gill filaments. SS-14-I inhibited the expression of IGFR1 mRNAs in filaments incubated in vitro in a time- and dose-dependent manner; the ED50 for inhibition of both IGFR1A and IGFR1B mRNAs was ca. 5 ng/ml and the maximal response occurred after 6h. The N-terminally extended form of SS-14-I, SS-28-I, as well as the N-terminally extended [Tyr7, Gly10]-substituted forms of SS, SS-25-II and SS-28-II, also inhibited expression of both IGFR1 mRNAs. The 14-amino acid [Tyr7, Gly10]-substituted form of SS, SS-14-II, did not affect the expression of IGFR1A, but inhibited the expression of IGFR1B. SS-14-I also inhibited 125I-IGF-I binding capacity in microsomes prepared from gill filaments incubated in vitro, but had no effect on binding affinity. The mechanism of SS-14-I-inhibited IGFR expression also was studied. SS-14-I increased the phosphorylation of MAPK and Akt in a time- and dose-dependent manner. MAPK and Akt inhibitors blocked SS-14-I inhibition of IGFR mRNA expression. These data indicate that SS-14-I inhibits mRNA and functional expression of IGFR1s and that SS-14-inhibited IGFR1 mRNA expression involves activation of the MAPK and Akt/PI3K pathways. (Supported by NSF grant IOB 0444860 to M.A.S.)
