REGULATION OF HYPOTHALAMIC SOMATOSTATIN, GROWTH HORMONE-RELEASING HORMONE, AND GROWTH-HORMONE RECEPTOR MESSENGER-RIBONUCLEIC-ACID BY GLUCOCORTICOIDS

Although it is well known that chronic treatment with glucocorticoids inhibits somatic growth, the mechanism of action of this inhibitory ef fect is not completely understood. It is likely that glucocorticoids a ct at various levels, including pituitary, hypothalamus, and periphera l organs modulating GH synthesis, secretion, and action. In this work, we evaluated the effect of dexametbasone on hypothalamic somatostatin and GH-releasing hormone (GHRH) messenger RNA (mRNA) levels by in sit u hybridization. We found a significant decrease of somatostatin mRNA content in the periventricular nucleus of the hypothalamus after 3, 8, and 15 days of treatment with dexamethasone. Furthermore, we observed a reduction in GHRH mRNA levels in the arcuate nucleus after 8 and 15 days of treatment with this steroid. As it has been shown that GH fee ds back to regulate somatostatin and GHRH expression at the hypothalam ic level through high affinity GH receptors, we evaluated the possibil ity of a GH-mediated action in the inhibitory effect of glucocorticoid s on somatostatin and GHRH mRNA levels. To address this issue, we firs t studied the GH receptor mRNA content in both the periventricular and arcuate nuclei of the hypothalamus after dexamethasone treatment. Sec ondly, the effect of dexamethasone on somatostatin and GHRH mRNA level s in hypophysectomized animals also was assessed. We found a significa nt decrease in GH receptor mRNA levels in the periventricular nucleus and in the arcuate nucleus after 1, 3, 8, and 15 days of glucocorticoi d administration. Finally, in hypophysectomized rats, dexamethasone tr eatment for 15 days did not reduce somatostatin mRNA levels in the per iventricular nucleus but significantly decreased GHRH mRNA content in the arcuate nucleus. In summary, our results suggest an inhibitory GH- mediated effect of dexamethasone on somatostatin mRNA levels in the pe riventricular nucleus and an inhibitory direct effect of dexamethasone on GHRH neurones in the arcuate nucleus.