Molecular genetics of growth hormone-releasing factors

To elucidate the effects of GRF on GH synthesis and of the GH-IGF-I axis on hypothalamic GRF synthesis, we measured the mRNA levels of hypothalamic GRF and pituitary GH in pubertal male rats treated for 3 weeks with antirat GRF gamma-globulin (GRF-ab), antisomatostatin gamma-globulin (SRIF-ab) or both. Immunoneutralization of circulating endogenous GRF resulted in a marked decrease in serum IGF-I and pituitary GH mRNA levels in Northern blot analysis, whereas it significantly increased GRF mRNA levels in the arcuate nucleus in both Northern blot and in situ hybridization analysis. Immunoneutralization of circulating endogenous SRIF failed to affect GRF mRNA levels but caused a slight reduction in pituitary GH mRNA. Then, we examined the effect of systemic replacement with rat GH or IGF-I for 1 week on GRF mRNA levels in the hypothalamus of rats treated with GRF-ab for 2 weeks. Replacement with either rat GH or IGF-I significantly suppressed the increased hypothalamic GRF mRNA levels. These data indicate that endogenous GRF is essential in normal synthesis of pituitary GH and that both GH and IGF-I negatively regulate the synthesis of hypothalamic GRF.