The effects of octreotide on GH receptor and IGF-I expression in the GH-deficient rat

Somatostatin has been suggested to influence the somatotrophic axis outside the central nervous system, in reducing GH-induced IGF-I mRNA and IGF-I generation. This study aimed to determine whether such effects were mediated via the GH receptor (GHR). GH-deficient dwarf rats aged 45-47 days (n=8 per group) received twice daily subcutaneous injections of octreotide (1 mg/kg) (group O), saline (group S), octreotide (1 mg/kg) plus bovine GH (0.25 mg/kg) (group OG), or bovine GH (0.25 mg/kg) plus saline (group G) for 10 days. Octreotide-treated animals had less weight gain compared with saline-treated animals, but not when GH cotreated (group OG vs G). Octreotide had an overall effect on decreasing length gain (P<0.01). Serum IGF-I (ng/ml) was reduced by octreotide (group O 171+/-11, group S 239 +/- 20, P<0.01; group OG 283 +/- 30, group G 362 +/- 10, P<0.001), as was serum insulin (P<0.001). A significant decrease in hepatic and muscle IGF-I mRNA expression was found as expected, yet this was not associated with decreased hepatic GHR expression. Rather, an increase in hepatic I-125-bovine GH specific binding was observed (P<0.001) and, in GH-cotreated animals (OG), hepatic GHR and GH binding protein (GHBP) mRNA expression were also increased by octreotide by approximately 40%. In muscle, octreotide was associated with an approximately 30% decrease in GHBP mRNA and no effect on GHR mRNA. This study suggests that the suppressive effects of octreotide on IGF-I metabolism, at least in liver, are not mediated via down-regulation of GHR expression, but more likely by direct effects on IGF-I expression.