Insulin-like growth factor I modulates hypothalamic somatostatin through a growth hormone releasing factor increased somatostatin release and messenger ribonucleic acid levels

Abstract

Insulin-like growth factor I (IGF-I) has been shown to participate in feedback inhibition of growth hormone (GH) secretion at the level of both the pituitary and hypothalamus. Therefore, we tested the possible involvement of IGF-I on somatostatin (SRIF) and GH-releasing factor (GRF) release in median eminence (ME) fragments and periventricular nucleus (PeN) of male rats. The levels of SRIF messenger ribonucleic acid (mRNA) were also determined in PeN incubated in vitro with IGF-I. The ME's were incubated in Krebs-Ringer bicarbonate glucose buffer in the presence of various concentrations of IGF-I (10 −7 to 10 −11 M) for 30 min. SRIF and GRF released into the medium were quantitated by RIA. The release of SRIF and GRF from the ME's was stimulated significantly ( P < 0.025 and P < 0.05, respectively) by 10 −9 M IGF-I. To determine whether the effect of IGF-I on SRIF release is mediated by GRF release in the ME, a specific GRF antibody (ab) (1 : 500) was used concomitantly with IGF-I (10 −9 M). The release of SRIF induced by IGF-I was blocked by the GRF ab ( P < 0.001), but not by normal rabbit serum used at the same dilution. To determine the effect of IGF-I on the regulation of SRIF mRNA levels, SRIF mRNA was determined in PeN explants incubated in the presence of IGF-I (10 −8 to 10 −10 M) for 2 to 6 h. Levels of SRIF mRNA were determined by a S 1 nuclease protection assay using a 32P-labelled rat SRIF riboprobe. IGF-I (10 −8 M) caused a significant increase in SRIF mRNA levels ( P < 0.05) at 6 h of incubation. This effect of IGF-I on SRIF mRNA was also blocked by GRF ab. IGF-I (10 −8 M) stimulated significantly the release of SRIF from the PeN at 30 min and 6 h. GRF release was increased significantly by 10 −10 M and 10 −8 M IGF at 30 min and 6 h, respectively. These results suggest that the effect of IGF-I on SRIF release is due to its combined effects on GRF-mediated SRIF release and increased SRIF mRNA levels.