Concomitant infusion of ovine corticotropin-releasing hormone does not prevent suppression of the hypothalamus-pituitary-adrenal axis by dexamethasone in male rats.

Abstract

Glucocorticoids (GCs) suppress the hypothalamus-pituitary-adrenal (HPA) axis at various sites including hypothalamus, pituitary and extrahypothalamic brain. Previous studies have shown that corticotropin-releasing hormone (CRH) and vasopressin facilitate the recovery of HPA axis suppressed by GCs. In this study, we investigate whether the concomitant continuous infusion of CRH may prevent the suppression of HPA axis by GCs. Groups of male Wistar rats weighing 140 to 160 g were implanted subcutaneously with Alzet osmotic pump for delivery of dexamethasone (DEX), 2 micrograms/h and/or CRH, 0.66 microgram/h. Control rats were implanted with sialistic tube of similar size. Rats were decapitated 3 or 7 days after osmotic pump implantation. In spite of the suppression of plasma corticosterone, the body weight (BW), adrenal weight (AW), plasma corticotropin (ACTH) and pituitary ACTH content of rats treated with DEX for 3 days were not significantly different from those of control rats. Concomitant infusion of ovine CRH (oCRH) and DEX for 3 days caused impaired BW gain, adrenal atrophy in addition to further reduction of plasma corticosterone. Treatment with DEX and/or oCRH for 7 days caused further suppression of HPA axis as shown by reduced pituitary ACTH content. In conclusion, simultaneous infusion of oCRH and DEX does not prevent and may even worsen HPA axis suppression by DEX.