Insulin-like growth factor I action on rat anterior pituitary cells: suppression of growth hormone secretion and messenger ribonucleic acid levels.
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-(1-44) (GHRH; 1 nM) stimulated GH secretion by 230% during 72 h. IGF-I (0.13 nM) suppressed GHRH-stimulated GH secretion by 30% (P less than 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 GHRH-stimulated 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-I-treated 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.
Yamashita
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D000818:Animals; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000494:pharmacology*
D007328:Insulin; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D005947:Glucose