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ESCAPE FROM DEXAMETHASONE‐INDUCED ACTH AND CORTISOL SUPPRESSION BY CORTICOTROPHIN‐RELEASING HORMONE: MODULATORY EFFECT OF BASAL DEXAMETHASONE LEVELS
Author(s) -
HERMUS A. R. M. M.,
PIETERS G. F. F. M.,
PESMAN G. J.,
HOFMAN J.,
SMALS A. G. H.,
BENRAAD TH.J.,
KLOPPENBORG P. W. C.
Publication year - 1987
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1987.tb03640.x
Subject(s) - dexamethasone , medicine , endocrinology , evening , glucocorticoid , basal (medicine) , corticotropin releasing hormone , corticosteroid , adrenocorticotropic hormone , hydrocortisone , hormone , physics , astronomy , insulin
SUMMARY The response of ACTH and Cortisol to corticotrophin‐releasing hormone (CRH) after pretreatment with various doses of dexamethasone was investigated in five healthy subjects. The five subjects participated in six experiments. In each experiment 200 μg ovine CRH was administered as an i.v. bolus injection at 0900 h after pretreatment with respectively: (A) 1 mg dexamethasone orally at 2300 h in the evening before CRH injection, (B) 2 mg dexamethasone orally at 2300 h in the evening before CRH injection, (C) 4 mg dexamethasone orally at 2300 h in the evening before CRH injection, (D) 2 mg dexamethasone orally at 2300 h in the evening before CRH injection, followed by 2 mg dexamethasone orally 1 h before CRH, (E) no dexamethasone and (F) 1 mg dexamethasone orally 1 h before CRH injection. In spite of overnight suppression with a single dose of dexamethasone CRH elicited Cortisol rises in all individuals (experiments A‐C). Dexamethasone pretreatment in experiment D abolished the CRH‐induced stimulation of the pituitary‐adrenal axis. There was a significant and negative correlation between the basal dexamethasone levels (i.e. the dexamethasone levels immediately before CRH administration) in the experiments A‐D and the areas under the individual ACTH ( R =−0.62; P < 0.01 by Spearman's rank correlation test) and Cortisol ( R =−0.81; P < 0.001 by Spearman's test) curves, i.e. the lower the basal dexamethasone levels, the greater the rise in ACTH and Cortisol levels after CRH administration. Pretreatment with a single dose of 1 mg dexamethasone 1 h before CRH injection (experiment F) led to a significant inhibition of the CRH‐induced ACTH and Cortisol response, despite unsuppressed pre‐CRH ACTH and Cortisol levels. We conclude that CRH is able to overrule the inhibition of the pituitary‐adrenal axis by overnight suppression with pharmacological doses of dexamethasone. The strongly negative correlation between the basal dexamethasone levels and the CRH‐induced pituitary‐adrenal responses suggests that circulating glucocorticoid levels modulate the response of ACTH and Cortisol to CRH.