EFFECTS OF SHORT-AND LONG-TERM DEXAMETHASONE TREATMENT ON GROWTH AND GROWTH-HORMONE (GH)-RELEASING HORMONE (GRH)-GH-INSULIN-LIKE GROWTH-FACTOR-I AXIS IN CONSCIOUS RATS

Although the inhibitory effects of a chronic excess of glucocorticoids (GC) on body growth and GH secretion are well established, the mechan isms involved remain unclear. In this study, we examined the chronic e ffects of a high dose of dexamethasone (DEX) on spontaneous GH secreti on and insulin-like growth factor (IGF)-I in conscious rats. The anima ls were given daily ip injections of DEX (200 mu g/day) for either one or four weeks. Body growth assessed by tibia length and serum IGF-I l evels was significantly inhibited 1 week after treatment. By contrast, spontaneous GH secretion was not altered 1 week after the treatment. Neither hypothalamic GRH and somtatostain mRNA levels nor GH responses to GRH from single somatotropes were affected 1 week after the treatm ent. Four weeks after DEX treatment, body growth of the rats was notic eably suppressed. Interestingly, spontaneous GH secretion, hypothalami c GRH mRNA levels and GH responses to GRH were all inhibited 4 weeks a fter treatment. Pituitary GRH receptor mRNA levels were not altered 1 week after treatment, but increased after 4 weeks. These results indic ate that a high dose of DEX initially impairs IGF-I production and sub sequently inhibits spontaneous GH secretion in rats. Inhibition of spo ntaneous GH secretion resulting from chronic GC excess is due, at leas t in part, to the impairment of hypothalamic GRH synthesis and pituita ry GH responsiveness. An increase in the pituitary GRH receptor may be caused by decreased GRH secretion.