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 µg/h and/or CRH, 0.66 µg/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.
Similar content being viewed by others
References
Axelrod L. Corticosteroid therapy In: Becker K.L., Bilezikian J.P., Lynn Loriaux D., et al. (Eds.), Principle and Practice of Endocrinology and Metabolism. J. B. Lippincott Company, Philadelphia, PA, 1990, p. 613.
Huang T.S. Corticotropin secretagogues facilitate recovery of the hypothalamus-pituitary-adrenal axis suppressed by prolonged treatment with dexamethasone. Metabolism 43: 544, 1994.
Keller-Wood M.E., Dallman M.F. Corticosteroid inhibition of ACTH secretion. Endocr. Rev. 5: 1, 1984.
Von Bardeleben U., Holsborer F., Stalla G.K., Muller O.A. Combined administration of human corticotropin-releasing factor and lysine vasopressin induces cortisol escape from dexamethasone suppression in healthy subjects. Life Sci. 37: 1613, 1985.
Geltz B.J., Contreras L.N., McComb D.J., Kovacs K., Tyrrell J.B., Dallman M.F. Chronic administration of corticotropin-releasing factor increases pituitary corticotroph number. Endocrinology 120: 381, 1987.
Calogero A.E., Gallucci W.T., Gold P.W., Chrousos G.P. Multiple regulatory feedback loops upon rat hypothalamic corticotropin-releasing hormone secretion in vitro: Potential clinical implications. J. Clin. Invest. 82: 767, 1988.
De Kloet E.R., Van Der View J., De Wied D. The site of the suppression of dexamethasone on pituitary-adrenal activity. Endocrinology 94: 61, 1974.
Jingami H., Matsukura S., Numa S., Imura H. Effects of adrenalectomy and dexamethasone administration on the level of propre-corticotropin-releasing factor messenger ribonucleic acid (mRNA) in the hypothalamus and adrenocorticotropin/β-lipotropin precursor mRNA in the pituitary in rats. Endocrinology 117: 1314, 1985.
Carnes M., Barksdalc C.M., Kalin N.H., Brownfield M.S., Lent S.J. Effects of dexamethasone on central and peripheral ACTH systems in the rat. Neuroendocrinology 45: 160, 1987.
Sapolsky R.M., Krey L.C., McEwen B.S. The neuroendocrinology of stress and aging: The glucocorticoid cascade hypothesis. Endocr. Rev. 7: 284, 1986.
Kingge K.M. Adrenocortical response to stress in rats with lesions in hippocampus and amygdala. Proc. Soc. Exp. Biol. Med. 108: 18, 1961.
Graber A.L., Ney R.L., Nicholson W.E., Island D.P., Liddle G.W. Natural history of pituitary-adrenal recovery following long-term suppression with corticosteroids. J. Clin. Endocrinol. Metab. 25: 11, 1965.
Wyml P.C., Harwood J.P., Catt K.J., Aguilera G. Corticotropin-releasing factor (CRF) induces desensitization of the rat pituitary CRF receptor-adenyl cyclase complex. Endocrinology 122: 351, 1988.
Rivier C., Vale W. Effect of the long-term admimistration of corticotropin-releasing factor on the pituitary-adrenal and pituitary-gonadal axis in the male rat. J. Clin Invest. 75: 689, 1985.
Wynn P.C., Harwood JP., Catt K.J., Aguilera G. Regulation of corticotropin-releasing factor (CRF) receptors in the rat pituitary gland: effects of adrenalectomy on CRF receptors and corticotroph responses. Endocrinology 116: 653, 1985.
Tizabi Y., Aguilera G. Desensitization of the hypothalamus-pituitary-adrenel axis following prolonged administration of corticotropin-releasing hormone or vasopressin. Neuroendocrinology 56: 611, 1992.
Haugen H.L., Millan M.A., Catt K.J., Aguilera G. Differential regulation of brain and pituitary corticotropin-releasing factor receptors by corticosterone. Endocrinology 120: 1527, 1987.
Mendelsolm F.A.O., Coyd C.J., Kachel C., Funder J.W. Glucocorticoid induction of angiotensin converting enzyme production from bovine endothelial cell in culture and rat lung in vivo. Clin. Exp. Pharmacol. Physiol. 7(Suppl. 1): 57, 1982.
Hauger R.L., Aguilera G. Regulation of pituitary corticotropin releasing hormone (CRH) receptors by CRH: interaction with vasopressin. Endocrinology 133: 1708, 1993.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Huang, TS. Concomitant infusion of ovine corticotropin-releasing hormone does not prevent suppression of the hypothalamus-pituitary-adrenal axis by dexamethasone in male rats. J Endocrinol Invest 20, 393–396 (1997). https://doi.org/10.1007/BF03347990
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03347990