Insulin regulation of rat growth hormone gene expression.
Insulin has been shown previously to inhibit basal and glucocorticoid- or T3-stimulated rat GH (rGH) synthesis, secretion, and mRNA levels in cultured rat pituitary tumor cells (GH3 cells) or pituitaries. The effects of insulin on rGH gene expression in GH3 cells were examined in greater detail in the current studies. Cells were deinduced for 5 days in medium devoid of steroids, T3, and insulin. Cells were then treated for 48 h with insulin (5 X 10(-9) M), dexamethasone (Dex; 10(-6) M), T3 (10(-8) M), insulin plus Dex, or insulin plus T3. When media and hormones were not replaced daily the results were similar to those obtained previously. Insulin decreased both basal and glucocorticoid-stimulated rGH mRNA levels to approximately 70% of control levels, as measured by cytoplasmic dot hybridization. By contrast, when media and hormones were replaced daily, rGH mRNA levels increased by 1.5 to 7-fold in response to insulin in the absence or presence of Dex or T3, measured by both cytoplasmic dot hybridization and RNA (Northern) blotting. Dex increased rGH mRNA levels under both sets of conditions, verifying the specific nature of the insulin influence. Maximum rGH gene expression was achieved after a 48-h exposure to insulin. The observed insulin effects were probably mediated through insulin rather than insulin-like growth factor I or II receptors, since the concentration of insulin employed was near the Kd of the hormone for its receptor measured in the same cells. These results suggest that insulin is capable of regulating rGH gene expression. The action of insulin can be either positive or negative and is influenced by the metabolic state of the cell.
D000818:Animals; D002460:Cell Line; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D013006:Growth Hormone / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014284:Triiodothyronine / Q000494:pharmacology
D003470:Culture Media; D007328:Insulin; D012333:RNA, Messenger; D014284:Triiodothyronine; D003907:Dexamethasone; D013006:Growth Hormone