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

Journal of Endocrinological Investigation volume 20, pages 393–396 (1997)Cite this article

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.

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References

  1. 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.

    Google Scholar 

  2. Huang T.S. Corticotropin secretagogues facilitate recovery of the hypothalamus-pituitary-adrenal axis suppressed by prolonged treatment with dexamethasone. Metabolism 43: 544, 1994.

    CAS  PubMed  Article  Google Scholar 

  3. Keller-Wood M.E., Dallman M.F. Corticosteroid inhibition of ACTH secretion. Endocr. Rev. 5: 1, 1984.

    CAS  PubMed  Article  Google Scholar 

  4. 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.

    Article  Google Scholar 

  5. 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.

    Article  Google Scholar 

  6. 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.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  7. 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.

    PubMed  Article  Google Scholar 

  8. 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.

    CAS  PubMed  Article  Google Scholar 

  9. 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.

    CAS  PubMed  Article  Google Scholar 

  10. Sapolsky R.M., Krey L.C., McEwen B.S. The neuroendocrinology of stress and aging: The glucocorticoid cascade hypothesis. Endocr. Rev. 7: 284, 1986.

    CAS  PubMed  Article  Google Scholar 

  11. Kingge K.M. Adrenocortical response to stress in rats with lesions in hippocampus and amygdala. Proc. Soc. Exp. Biol. Med. 108: 18, 1961.

    Article  Google Scholar 

  12. 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.

    CAS  PubMed  Article  Google Scholar 

  13. 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.

    Article  Google Scholar 

  14. 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.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  15. 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.

    Article  Google Scholar 

  16. Tizabi Y., Aguilera G. Desensitization of the hypothalamus-pituitary-adrenel axis following prolonged administration of corticotropin-releasing hormone or vasopressin. Neuroendocrinology 56: 611, 1992.

    CAS  PubMed  Article  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. 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.

    Google Scholar 

  19. Hauger R.L., Aguilera G. Regulation of pituitary corticotropin releasing hormone (CRH) receptors by CRH: interaction with vasopressin. Endocrinology 133: 1708, 1993.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, College of Medicine, National Taiwan University Hospital, 7 Chung-Shan S Road, Taipei, Taiwan, Republic of China

    Tien-Shang Huang M.D.

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  1. Tien-Shang Huang M.D.
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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

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  • DOI: https://doi.org/10.1007/BF03347990

Key-words

  • Glucocorticoids
  • hypothalamus-pituitary-adrenal axis
  • corticotropin-releasing hormone
  • down-regulation