Effects of Short- and Long-Term Dexamethasone Treatment on Growth and Growth Hormone (GH)-Releasing Hormone (GRH)-GH-Insulin-Like Growth Factor-l Axis in Conscious Rats.

Abstract

Abstract. Although the inhibitory effects of a chronic excess of glucocorticoids (GC) on body growth and GH secretion are well established, the mechanisms involved remain unclear. In this study, we examined the chronic effects of a high dose of dexamethasone (DEX) on spontaneous GH secretion and insulin-like growth factor (IGF)-I in conscious rats. The animals were given daily ip injections of DEX (200 µg/day) for either one or four weeks. Body growth assessed by tibia length and serum IGF-I levels 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 treatment. Four weeks after DEX treatment, body growth of the rats was noticeably suppressed.Interestingly, spontaneous GH secretion, hypothalamic GRH mRNA levels and GH responses to GRH were all inhibited 4 weeks after treatment. Pituitary GRH receptor mRNA levels were not altered 1 week after treatment, but increased after 4 weeks. These results indicate that a high dose of DEX initially impairs IGF-I production and subsequently inhibits spontaneous GH secretion in rats. Inhibition of spontaneous GH secretion resulting from chronic GC excess is due, at least in part, to the impairment of hypothalamic GRH synthesis and pituitary GH responsiveness. An increase in the pituitary GRH receptor may be caused by decreased GRH secretion.

Insulin-like growth factor I prevents corticosteroid-induced diaphragm muscle atrophy in emphysematous hamsters

“…By contrast, total serum IGF-I levels were similar between EMP-T-IGF-I and EMP-T animals, although still significantly lower than in EMP hamsters. CS-induced decrement in serum IGF-I has previously been reported by a number of other groups (39,53).…”

IGF-I regulates pro-opiomelanocortin and GH gene expression in the mouse pituitary gland

“…Glucocorticoids, e.g. DEX, are potent inhibitors of linear growth and GH secretion when secreted or administered in pharmacological amounts in vivo (Luo & Murphy 1989, Ohyama et al 1997. DEX inhibited GHRH expression in the hypothalamus, but increased GH expression (Evans et al 1982, Lam & Srivastava 1997.…”

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“…[64][65][66] In addition, the IGF system is modulated by GCs or stress under normal glycemic conditions in both animals and man. [67][68][69][70]…”