Skip to main content
Journal of the National Medical Association logoLink to Journal of the National Medical Association
letter
. 1977 Dec;69(12):873–878.

Suppression of the Hypothalamic-Pituitary-Adrenal Axis after Subcutaneous Cortisone Acetate Administration in Rats

Robert B Mims
PMCID: PMC2537021  PMID: 224195

Abstract

Groups of female rats were injected daily for 14 days with 10 mg of cortisone acetate subcutaneously, to study the mechanisms of glucocorticoid suppression on the hypothalamic-pituitary-adrenal axis. Pituitary adrenocorticotropic hormone (ACTH) content, plasma ACTH, adrenal venous corticosterone, adrenal weights, and the catabolic effects on body weight were studied simultaneously (under stressful and non-stressful conditions) before, during, and up to six weeks after cortisone. This study confirmed the results of other investigators that cortisone acetate caused catabolic weight loss and adrenal atrophy, but it was noted to persist up to six weeks after the injections. Glucocorticoid acetate was more effective in causing ACTH-axis suppression than succinate or phosphate preparations, and the effects were dose and time related. Significant depletion of pituitary ACTH content, suppression of plasma ACTH, and corticosterone secretion occurred five to seven days after beginning cortisone acetate (p=<0.001); it was continuous throughout the injection schedule (p=<0.001); it remained for two to four weeks after the cortisone was discontinued (p=<0.001). The animals showed minimum plasma ACTH responsiveness to severe acute stress during this two to four-week suppression phase, but rapid recovery occurred thereafter. Plasma ACTH was undetectable up to six weeks post-cortisone when the animals were not under stress. This may be related to residual cortisone acetate found at the injection sites, or to an altered or different ACTH-axis control mechanism. The sequence of events during recovery from cortisone suppression appeared to be (1) repletion of corticotrophin-releasing hormone (by inference), (2) repletion of pituitary ACTH content, (3) secretion of plasma ACTH, (4) reversal of adrenal atrophy, and (5) subsequent secretion of corticosterone.

Full text

PDF
873

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ackerman G. L., Nolsn C. M. Adrenocortical responsiveness after alternate-day corticosteroid therapy. N Engl J Med. 1968 Feb 22;278(8):405–409. doi: 10.1056/NEJM196802222780801. [DOI] [PubMed] [Google Scholar]
  2. BIRMINGHAM M. K., KURLENTS E., ROCHEFORT G. J., SAFFRAN M., SCHALLY A. V. ACTH content of rat pituitary glands. Endocrinology. 1956 Dec;59(6):677–680. doi: 10.1210/endo-59-6-677. [DOI] [PubMed] [Google Scholar]
  3. Byyny R. L. Withdrawal from glucocorticoid therapy. N Engl J Med. 1976 Jul 1;295(1):30–32. doi: 10.1056/NEJM197607012950107. [DOI] [PubMed] [Google Scholar]
  4. COLLINS E. J., OLSON K. J. Inhibition of steroid-induced adrenal hypofunction. Proc Soc Exp Biol Med. 1954 Oct;87(1):76–78. doi: 10.3181/00379727-87-21290. [DOI] [PubMed] [Google Scholar]
  5. Cooper C. E., Nelson D. H. ACTH LEVELS IN PLASMA IN PREOPERATIVE AND SURGICALLY STRESSED PATIENTS. J Clin Invest. 1962 Aug;41(8):1599–1605. doi: 10.1172/JCI104618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DANOWSKI T. S., BONESSI J. V., SABEH G., SUTTON R. D., WEBSTER M. W., Jr, SARVER M. E. PROBABILITIES OF PITUITARY-ADRENAL RESPONSIVENESS AFTER STEROID THERAPY. Ann Intern Med. 1964 Jul;61:11–26. doi: 10.7326/0003-4819-61-1-11. [DOI] [PubMed] [Google Scholar]
  7. FARRELL G. L., LAQUEUR G. Reduction of pituitary content of ACTH by cortisone. Endocrinology. 1955 Apr;56(4):471–473. doi: 10.1210/endo-56-4-471. [DOI] [PubMed] [Google Scholar]
  8. FRASER C. G., PREUSS F. S., BIGFORD W. D. Adrenal atrophy and irreversible shock associated with cortisone therapy. J Am Med Assoc. 1952 Aug 23;149(17):1542–1543. doi: 10.1001/jama.1952.72930340001009. [DOI] [PubMed] [Google Scholar]
  9. 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. 1965 Jan;25:11–16. doi: 10.1210/jcem-25-1-11. [DOI] [PubMed] [Google Scholar]
  10. HARTER J. G., REDDY W. J., THORN G. W. STUDIES ON AN INTERMITTENT CORTICOSTEROID DOSAGE REGIMEN. N Engl J Med. 1963 Sep 19;269:591–596. doi: 10.1056/NEJM196309192691201. [DOI] [PubMed] [Google Scholar]
  11. HODGES J. R., VERNIKOS J. A comparison of the pituitary inhibitory effects of prednisone, prednisolone, and hydrocortisone. Br J Pharmacol Chemother. 1958 Mar;13(1):98–102. doi: 10.1111/j.1476-5381.1958.tb00199.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HOLUB D. A., KITAY J. I., JAILER J. W. Effects of exogenous adrenocorticotropic hormone (ACTH) upon pituitary ACTH concentration after prolonged cortisone treatment and stress. J Clin Invest. 1959 Feb;38(2):291–298. doi: 10.1172/JCI103801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ingle D. J., Kendall E. C. ATROPHY OF THE ADRENAL CORTEX OF THE RAT PRODUCED BY THE ADMINISTRATION OF LARGE AMOUNTS OF CORTIN. Science. 1937 Sep 10;86(2228):245–245. doi: 10.1126/science.86.2228.245. [DOI] [PubMed] [Google Scholar]
  14. LIPSCOMB H. S., NELSON D. H. A sensitive biologic assay for ACTH. Endocrinology. 1962 Jul;71:13–23. doi: 10.1210/endo-71-1-13. [DOI] [PubMed] [Google Scholar]
  15. Mims R. B. Plasma ACTH in the adrenalectomized rat. Horm Metab Res. 1973 Sep;5(5):368–371. doi: 10.1055/s-0028-1093925. [DOI] [PubMed] [Google Scholar]
  16. PARIS J. Pituitary-adrenal suppression after protracted administration of adrenal cortical hormones. Proc Staff Meet Mayo Clin. 1961 Jun 21;36:305–317. [PubMed] [Google Scholar]
  17. REED P. I., CLAYMAN C. B., PALMER W. L. ADRENOCORTICAL AND PITUITARY RESPONSIVENESS FOLLOWING LONG-TERM, HIGH DOSAGE CORTICOTROPIN ADMINISTRATION. Ann Intern Med. 1964 Jul;61:1–10. doi: 10.7326/0003-4819-61-1-1. [DOI] [PubMed] [Google Scholar]
  18. Rabhan N. B. Pituitary-adrenal suppression and Cushing's syndrome after intermittent dexamethasone therapy. Ann Intern Med. 1968 Dec;69(6):1141–1148. doi: 10.7326/0003-4819-69-6-1141. [DOI] [PubMed] [Google Scholar]
  19. SAYERS G., SAYERS M. A. The pituitary-adrenal system. Recent Prog Horm Res. 1948;2(1 VOL):81–115. doi: 10.1016/b978-1-4831-9892-7.50006-9. [DOI] [PubMed] [Google Scholar]
  20. SILBER R. H., BUSCH R. D., OSLAPAS R. Practical procedure for estimation of corticosterone or hydrocortisone. Clin Chem. 1958 Aug;4(4):278–285. [PubMed] [Google Scholar]
  21. TREADWELL B. L., SALVAGE O., SEVER E. D., COPEMAN W. S. Pituitary-adrenal function during corticosteroid therapy. Lancet. 1963 Feb 16;1(7277):355–358. doi: 10.1016/s0140-6736(63)91383-7. [DOI] [PubMed] [Google Scholar]
  22. VERNIKOS-DANELLIS J. EFFECT OF STRESS, ADRENALECTOMY, HYPOPHYSECTOMY AND HYDROCORTISONE ON THE CORTICOTROPIN-RELEASING ACTIVITY OF RAT MEDIAN EMINENCE. Endocrinology. 1965 Jan;76:122–126. doi: 10.1210/endo-76-1-122. [DOI] [PubMed] [Google Scholar]

Articles from Journal of the National Medical Association are provided here courtesy of National Medical Association

RESOURCES