Corticotropin secretagogues facilitate recovery of the hypothalamus-pituitary-adrenal axis suppressed by prolonged treatment with dexamethasone.
Prolonged use of glucocorticoids (GCs) can cause prolonged suppression of the hypothalamus-pituitary-adrenal (HPA) axis. This study examined the possibility that corticotropin or its secretagogues such as vasopressin, corticotropin-releasing hormone (CRH), or insulin accelerate recovery of the HPA axis after prolonged treatment with dexamethasone (DEX). Suppression of the HPA axis was induced in rats by DEX at a dosage of 250 micrograms/100 g body weight (BW)/d for 14 days, after which rats were administered saline, corticotropin (Cortrosyn 0.1 mg), ovine CRH (oCRH 6 micrograms), vasopressin (2 U), or insulin (2 U) each morning. Adrenal weight (AW), BW, plasma corticosterone, and corticotropin, as well as pituitary corticotropin content, decreased significantly after DEX treatment. The plasma corticotropin level was significantly elevated 7 days after discontinuation of DEX treatment (day 8) and remained so until day 11, whereas the pituitary corticotropin content had returned to normal on day 8. Plasma corticosterone was suppressed until day 8, but was not significantly different from normal on day 11. The AW was also decreased until day 4, but was not different from normal on day 8 or day 11. The BW of experimental rats remained subnormal during the study period. Treatment of DEX-suppressed rats with exogenous corticotropin induced adrenal hyperplasia, but suppressed the plasma corticotropin level and delayed the normalization of plasma corticosterone until day 11. The insulin-treated group differed in no respect from the saline-treated group. Treatment with oCRH or vasopressin for 8 days normalized plasma and pituitary corticotropin, as well as plasma corticosterone. Hypothalamic immunoreactive CRH (iCRH) did not differ among any treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Huang
T S
TS
Department of Medicine, National Taiwan University Hospital, Taipei, Republic of China.
D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology*; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014667:Vasopressins / Q000494:pharmacology
D007328:Insulin; D014667:Vasopressins; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone