CHRONIC GROWTH-HORMONE (GH) HYPERSECRETION INDUCES RECIPROCAL AND REVERSIBLE CHANGES IN MESSENGER-RNA LEVELS FROM HYPOTHALAMIC GH-RELEASINGHORMONE AND SOMATOSTATIN NEURONS IN THE RAT

Effects of growth hormone (GH) hypersecretion on somatostatin-(SRIH) a nd GH-releasing hormone (GHRH) were studied by in situ hybridization a nd receptor autoradiography in rats bearing a GH-secreting tumor. 6 an d 18 wk after tumor induction, animals displayed a sharp increase in b ody weight and GH plasma levels; pituitary GH content was reduced by 4 7 and 55%, while that of prolactin and thyrotropin was unchanged. At 1 8 wk, hypothalamic GHRH and SRIH levels had fallen by 84 and 52%, resp ectively. In parallel, the density of GHRH mRNA per arcuate neuron was reduced by 52 and 50% at 6 and 18 wk, while SRIH mRNA levels increase d by 71 and 83% in the periventricular nucleus (with no alteration in the hilus of the dentate gyrus). The numbers of GHRH- and SRIH-synthet izing neurons in the hypothalamus were not altered in GH-hypersecretin g rats. Resection of the tumor restored hypothalamic GHRH and SRIH mRN As to control levels. GH hypersecretion did not modify I-125-SRIH bind ing sites on GHRH neurons. Thus, chronic GH hypersecretion affects the expression of the genes encoding for GHRH and SRIH. The effect is lon g lasting, not desensitizable and reversible.