Insulin-Like Growth Factor I Action on Rat Anterior Pituitary Cells: Suppression of Growth Hormone Secretion and Messenger Ribonucleic Acid Levels*

Publisher Website
Google Scholar
Abstract
Somatomedin preparations have previously been shown to suppress GH release. The effects of a synthetic recombinant human insulin-like growth factor analog (IGF-I; Thr 59) were, therefore, tested on long term GH secretion by male rat pituitary monolayer cell cultures grown in serum-free defined medium. IGF-I (3.25 nm) maximally suppressed basal GH secretion for up to 72 h by 66%, with an ED50 of 0.1 nm. Human pancreatic GRF-(l–44) (GHRH; 1 nm) stimulated GH secretion by 230% during 72 h. IGF-I (0.13 nm) suppressed GHRHstimulated GH secretion by 30% (P < 0.005). IGF-I (0.625 nm) completely abolished stimulation of GH by GHRH (1 nm), while higher doses of IGF-I (up to 6.5 nm) actually suppressed GH secretion even in the presence of GHRH (up to 1 nm). The depletion of intracellular GH levels in GHRH-treated cells was reversed by IGF-I (3.25 nm). PRL secretion was not altered in the same cells by IGF-I. Equivalent doses of epidermal growth factor and fibroblast growth factor did not alter basal or GHRHstimulated GH secretion. Nitrocellulose dot hybridization of immobilized pituitary cell RNA extracts with rat GH [32P]cDNA showed that cellular GH mRNA levels were lowered in IGF-Itreated cells in a dose-dependent manner. Maximal suppression of GH mRNA was achieved with 0.65 nm IGF-I. IGF-I also inhibited the 3-fold stimulation of GH mRNA induced by 1 nm GHRH. The data show that IGF-I directly modulates GH gene expression at the level of the somatotroph by inhibiting basal and GHRH-stimulated GH secretion and GH mRNA levels during 72 h. These effects may occur at different postranscriptional sites. Alternatively, they may result from a direct inhibition of IGF-I on GH gene transcription. (Endocrinology118: 176-182,1986)