TY - JOUR
T1 - The ERK and PI3K signaling pathways mediate inhibition of insulin-like growth factor-1 receptor mRNA expression by somatostatin
AU - Hanson, Andrea
AU - Poudyal, Deepak
AU - Hagemeister, Alison
AU - Reindl, Katie M.
AU - Sheridan, Mark A.
PY - 2010/2/5
Y1 - 2010/2/5
N2 - Somatostatins (SSs) are a structurally diverse family of peptide hormones that regulate various aspects of growth, development, and metabolism in vertebrates. Previously, we showed that SSs inhibit mRNA and functional expression of insulin-like growth factor-1 receptors (IGFR1) in gill filaments of rainbow trout. In this study, we used trout gill filaments, which express in high abundance two distinct IGFR1s, IGFR1A and IGFR1B, to examine the mechanism(s) through which SSs exert their inhibitory effects on IGFR1 expression. SS-14, a predominat SS isoform, directly stimulated the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt), a downstream target of phosphatidylinositol 3-kinase (PI3K), in filaments incubated in vitro. Activation of ERK and Akt by SS-14 was rapid, occuring within 5-10 min, and was concentration-dependent. The ERK pathway inhibitor, U0126, retarded SS-14-stimulated phosphorylation of ERK 1/2, whereas the PI3K inhibitor, LY294002, blocked SS-14-stimulated phosphorylation of Akt. SS-14-inhibited expression of IGFR1 mRNAs was blocked by both U0126 and LY294002. These data indicate that SS-14 inhibition of IGFR1 mRNA expression is mediated through the ERK and PI3K/Akt signaling pathways.
AB - Somatostatins (SSs) are a structurally diverse family of peptide hormones that regulate various aspects of growth, development, and metabolism in vertebrates. Previously, we showed that SSs inhibit mRNA and functional expression of insulin-like growth factor-1 receptors (IGFR1) in gill filaments of rainbow trout. In this study, we used trout gill filaments, which express in high abundance two distinct IGFR1s, IGFR1A and IGFR1B, to examine the mechanism(s) through which SSs exert their inhibitory effects on IGFR1 expression. SS-14, a predominat SS isoform, directly stimulated the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt), a downstream target of phosphatidylinositol 3-kinase (PI3K), in filaments incubated in vitro. Activation of ERK and Akt by SS-14 was rapid, occuring within 5-10 min, and was concentration-dependent. The ERK pathway inhibitor, U0126, retarded SS-14-stimulated phosphorylation of ERK 1/2, whereas the PI3K inhibitor, LY294002, blocked SS-14-stimulated phosphorylation of Akt. SS-14-inhibited expression of IGFR1 mRNAs was blocked by both U0126 and LY294002. These data indicate that SS-14 inhibition of IGFR1 mRNA expression is mediated through the ERK and PI3K/Akt signaling pathways.
KW - Akt
KW - LY294002
KW - MAPK
KW - Rainbow trout
KW - U0126
UR - http://www.scopus.com/inward/record.url?scp=71849105524&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2009.09.034
DO - 10.1016/j.mce.2009.09.034
M3 - Article
C2 - 19815052
AN - SCOPUS:71849105524
SN - 0303-7207
VL - 315
SP - 57
EP - 62
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -