ONTOGENY OF GH MESSENGER-RNA AND GH SECRETION IN MALE AND FEMALE RATS- REGULATION BY GH-RELEASING HORMONE

Growth hormone-releasing hormone (GHRH) has been shown in vitro to inc rease proliferation of pituitary somatotrophs, to increase transcripti on of the GH gene, to promote accumulation of GH mRNA, and to stimulat e GH release. The in vivo involvement of hypothalamic GHRH in regulati ng GH mRNA content had never been clearly documented. We studied pitui tary GH mRNA and GH contents and serum concentrations of GH and insuli n-like growth factor I (IGF-I) in rats of both sexes during pubertal g rowth spurt and investigated the effects of GHRH deficiency (brought a bout by neonatal administration of monosodium glutamate, MSG) and exog enous GHRH administration on these parameters. In both sexes, GH mRNA content increased three- to fourfold between 4 and 12 wk of life and d eclined thereafter toward 33 wk of life. This was accompanied by virtu ally parallel changes in pituitary GH content and in serum IGF-I. Neon atal MSG abolished the pubertal increases in GH mRNA, pituitary GH, an d serum IGF-I and severely impaired growth rate. Exogenous GHRH (25 mu g/kg sc every 8 h for 7 days) given to intact animals between 6 and 7 wk of life significantly augmented pituitary GH mRNA content but was l ess effective in MSG-treated rats. We conclude that 1) pubertal growth spurt in both sexes is associated with rising pituitary GH mRNA conte nt; 2) GHRH deficiency abolishes the puberty-associated increase in GH synthesis and secretion and attenuates somatic growth rate; and 3) ex ogenous GHRH augments GH mRNA content. Thus puberty-associated augment ation of GHRH secretion is an important mechanism of somatic growth.