Regulation of GHRH receptor gene expression in the neonatal and adult rat pituitary.
The growth hormone releasing hormone (GHRH) receptor gene is essential for normal growth, and its expression is developmentally regulated. The factors that control GHRH receptor expression in the neonatal pituitary are not well understood. This study focuses on the regulation of GHRH receptor gene expression by thyroid hormone, glucocorticoids, insulin-like growth factor-I (IGF-I) and IGF-II in rat pituitary cell cultures. In newborn pituitaries, both T3 and hydrocortisone (24 h) caused a dose-dependent increase in GHRH receptor mRNA abundance, reaching levels 4.8-fold (P<0.001) and 6.5-fold (P<0.001) over corresponding controls. T3 and hydrocortisone also stimulated GHRH receptor expression in adult (70 day) pituitary cell cultures, consistent with our earlier findings. IGF-I treatment suppressed the inductive effects of T3 (P<0.02) and hydrocortisone (P<0.03) on GHRH receptor expression in adult pituitaries but not in neonatal pituitaries. Unlike IGF-I, IGF-II treatment had no effect on T3-induced or hydrocortisone-induced GHRH receptor expression in either neonates or adults. Taken together, these results indicate that (1) thyroid hormone and hydrocortisone act directly at the neonatal pituitary as potent stimulators of GHRH receptor gene expression, (2) IGF-I, but not IGF-II, acts at the pituitary to suppress GHRH receptor mRNA expression and (3) the effects of IGF-I on GHRH receptor gene expression are developmentally determined.
Korytko
A I
AI
Departments of Pediatrics and Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
Cuttler
L
L
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D005786:Gene Expression Regulation / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D010902:Pituitary Gland / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D011966:Receptors, LHRH / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology
D011966:Receptors, LHRH; D014284:Triiodothyronine; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D006854:Hydrocortisone