Somatostatin regulates hepatic growth hormone sensitivity by internalizing growth hormone receptors and by decreasing transcription of growth hormone receptor mRNAs

Abstract

Somatostatins (SSs), a diverse family of peptide hormones, have been shown to inhibit the release of growth hormone (GH) from the pituitary. In this study, we used rainbow trout to determine whether or not SSs affect growth in an extrapituitary manner, in particular, by decreasing GH sensitivity in liver. SS-14 significantly decreased hepatic GH binding in fish implanted (5.8 × 10−11 mol/h) for 15 days and in isolated hepatocytes. The processing of 125I-labeled trout GH (tGH) by isolated hepatocytes was investigated to determine whether or not the decrease in GH binding capacity resulted from receptor internalization. The internalization of 125I-labeled tGH was time dependent. By 6 h, 100 ng/ml SS-14 increased internalization of 125I-labeled tGH 58% over that observed in controls. Steady-state levels of mRNAs encoding the two hepatic growth hormone receptors (GHRs) of trout, GHR 1 and GHR 2, were measured to determine whether or not decreased GH binding capacity also resulted from decreased GHR synthesis. SS-14 directly inhibited steady-state levels of GHR 1 and GHR 2 mRNA in isolated hepatocytes in a concentration-dependent manner. The inhibitory effects of SS-14 on steady-state levels of GHR mRNAs resulted from reduced GHR mRNA transcription and not from altered mRNA stability. These results indicate that SSs regulate hepatic GH sensitivity by increasing GHR internalization and by altering GHR expression and suggest that SSs coordinate growth at the level of the pituitary, as well as at extrapituitary levels.