Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Feb;82(4):1247–1251. doi: 10.1073/pnas.82.4.1247

Evidence for a role of endogenous corticotropin-releasing factor in cold, ether, immobilization, and traumatic stress.

T Nakane, T Audhya, N Kanie, C S Hollander
PMCID: PMC397232  PMID: 2983331

Abstract

The role of corticotropin-releasing factor (CRF) in four model stresses (cold, ether, immobilization, and trauma) was examined in the guinea pig by using passive immunoneutralization with anti-CRF antiserum. Plasma corticotropin levels were measured at various times after exposure to stress, and groups treated with CRF antiserum were compared with those treated with normal rabbit serum. Of the four stresses tested, ether had the most pronounced effect on corticotropin secretion. Treatment with anti-CRF inhibited most of the ether-induced corticotropin secretory response, the difference between the normal serum- and the anti-CRF antiserum-treated groups being significant at 5 and 10 min (P less than 0.01). Corticotropin responses to cold stress in the two groups differed at the 0.05 level of significance at 10 and 20 min. After administration of trauma (leg fracture), a statistically significant difference (P less than 0.01) between the two groups also was evident, albeit only at 20 min. During immobilization, corticotropin levels differed significantly from control only in the normal serum-treated group but not in the anti-CRF-treated group. These findings show that CRF antiserum was effective in reducing corticotropin levels, indicating that CRF has an important role in mediating corticotropin response to stress. The fact that neutralization was incomplete might be due to an inability of the antiserum to sufficiently neutralize the endogenous CRF or, more likely, reflects the contribution of additional mediators, notably catecholamines and vasopressin, of corticotropin release upon stress.

Full text

PDF

Selected References

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

  1. BRODISH A. DIFFUSE HYPOTHALAMIC SYSTEM FOR THE REGULATION OF ACTH SECRETION. Endocrinology. 1963 Dec;73:727–735. doi: 10.1210/endo-73-6-727. [DOI] [PubMed] [Google Scholar]
  2. Brodish A. Extra-CNS corticotropin-releasing factors. Ann N Y Acad Sci. 1977 Oct 28;297:420–435. doi: 10.1111/j.1749-6632.1977.tb41873.x. [DOI] [PubMed] [Google Scholar]
  3. Brown M. R., Fisher L. A., Spiess J., Rivier C., Rivier J., Vale W. Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology. 1982 Sep;111(3):928–931. doi: 10.1210/endo-111-3-928. [DOI] [PubMed] [Google Scholar]
  4. Bruhn T. O., Plotsky P. M., Vale W. W. Effect of paraventricular lesions on corticotropin-releasing factor (CRF)-like immunoreactivity in the stalk-median eminence: studies on the adrenocorticotropin response to ether stress and exogenous CRF. Endocrinology. 1984 Jan;114(1):57–62. doi: 10.1210/endo-114-1-57. [DOI] [PubMed] [Google Scholar]
  5. Cook D. M., Kendall J. W., Greer M. A., Kramer R. M. The effect of acute or chronic ether stress on plasma ACTH concentration in the rat. Endocrinology. 1973 Nov;93(5):1019–1024. doi: 10.1210/endo-93-5-1019. [DOI] [PubMed] [Google Scholar]
  6. Daniels-Severs A., Goodwin A., Keil L. C., Vernikos-Danellis J. Effect of chronic crowding and cold on the pituitary-adrenal system: responsiveness to an acute stimulus during chronic stress. Pharmacology. 1973;9(6):348–356. doi: 10.1159/000136408. [DOI] [PubMed] [Google Scholar]
  7. GUILLEMIN R., ROSENBERG B. Humoral hypothalamic control of anterior pituitary: a study with combined tissue cultures. Endocrinology. 1955 Nov;57(5):599–607. doi: 10.1210/endo-57-5-599. [DOI] [PubMed] [Google Scholar]
  8. Gibbs F. P. Area of pons necessary for traumatic stress-induced ACTH release under pentobarbital anesthesia. Am J Physiol. 1969 Jul;217(1):84–88. doi: 10.1152/ajplegacy.1969.217.1.84. [DOI] [PubMed] [Google Scholar]
  9. Gibbs F. P. Central nervous system lesions that block release of ACTH caused by traumatic stress. Am J Physiol. 1969 Jul;217(1):78–83. doi: 10.1152/ajplegacy.1969.217.1.78. [DOI] [PubMed] [Google Scholar]
  10. Greer M. A., Rockie C. Inhibition by pentobarbital of ether-induced ACTH secretion in the rat. Endocrinology. 1968 Dec;83(6):1247–1252. doi: 10.1210/endo-83-6-1247. [DOI] [PubMed] [Google Scholar]
  11. Guillemin R., Vargo T., Rossier J., Minick S., Ling N., Rivier C., Vale W., Bloom F. beta-Endorphin and adrenocorticotropin are selected concomitantly by the pituitary gland. Science. 1977 Sep 30;197(4311):1367–1369. doi: 10.1126/science.197601. [DOI] [PubMed] [Google Scholar]
  12. Hedge G. A., van Ree J. M., Versteeg D. H. Correlation between hypothalamic catecholamine synthesis and ether stress-induced ACTH secretion. Neuroendocrinology. 1976;21(3):236–246. doi: 10.1159/000122528. [DOI] [PubMed] [Google Scholar]
  13. Hollander C. S., Audhya T., Nakane T., Kanie N., Kageyama N., Kuwayama A., Golbe L., Schlesinger D. Distribution, biosynthesis, and physiological role of corticotropin-releasing factor in the human: an overview. Trans Assoc Am Physicians. 1983;96:122–130. [PubMed] [Google Scholar]
  14. Hollander C. S., Audhya T., Russo M., Passarelli J., Nakane T., Schlesinger D. Levels of corticotropin releasing factor-like immunoreactivity in mammalian hypothalamic and extrahypothalamic brain tissue as determined with a monoclonal antibody to the ovine material. Endocrinology. 1983 Jun;112(6):2206–2208. doi: 10.1210/endo-112-6-2206. [DOI] [PubMed] [Google Scholar]
  15. Kant G. J., Bunnell B. N., Mougey E. H., Pennington L. L., Meyerhoff J. L. Effects of repeated stress on pituitary cyclic AMP, and plasma prolactin, corticosterone and growth hormone in male rats. Pharmacol Biochem Behav. 1983 Jun;18(6):967–971. doi: 10.1016/s0091-3057(83)80022-7. [DOI] [PubMed] [Google Scholar]
  16. Kant G. J., Mougey E. H., Pennington L. L., Meyerhoff J. L. Graded footshock stress elevates pituitary cyclic AMP and plasma beta-endorphin, beta-LPH corticosterone and prolactin. Life Sci. 1983 Dec 26;33(26):2657–2663. doi: 10.1016/0024-3205(83)90350-8. [DOI] [PubMed] [Google Scholar]
  17. Kvetñanský R., Kopin I. J., Saavedra J. M. Changes in epinephrine in individual hypothalamic nuclei after immobilization stress. Brain Res. 1978 Oct 27;155(2):387–390. doi: 10.1016/0006-8993(78)91035-1. [DOI] [PubMed] [Google Scholar]
  18. Langer P., Földes O., Kvetnanský R., Culman J., Torda T., El Daher F. Pituitary-thyroid function during acute immobilization stress in rats. Exp Clin Endocrinol. 1983 Jul;82(1):51–60. doi: 10.1055/s-0029-1210255. [DOI] [PubMed] [Google Scholar]
  19. Lenox R. H., Kant G. J., Sessions G. R., Pennington L. L., Mougey E. H., Meyerhoff J. L. Specific hormonal and neurochemical responses to different stressors. Neuroendocrinology. 1980 May;30(5):300–308. doi: 10.1159/000123018. [DOI] [PubMed] [Google Scholar]
  20. MATSUDA K., DUYCK C., KENDALL J. W., Jr, GREER M. A. PATHWAYS BY WHICH TRAUMATIC STRESS AND ETHER INDUCE INCREASED ACTH RELEASED IN THE RAT. Endocrinology. 1964 Jun;74:981–985. doi: 10.1210/endo-74-6-981. [DOI] [PubMed] [Google Scholar]
  21. Manev H., Pericić D. Hypothalamic GABA system and plasma corticosterone in ether stressed rats. Pharmacol Biochem Behav. 1983 Jun;18(6):847–850. doi: 10.1016/s0091-3057(83)80003-3. [DOI] [PubMed] [Google Scholar]
  22. Mason J. W. A historical view of the stress field. J Human Stress. 1975 Mar;1(1):6–contd. doi: 10.1080/0097840X.1975.9940399. [DOI] [PubMed] [Google Scholar]
  23. Mason J. W. A historical view of the stress field. J Human Stress. 1975 Jun;1(2):22–concl. doi: 10.1080/0097840X.1975.9940405. [DOI] [PubMed] [Google Scholar]
  24. Morley J. E., Levine A. S. Corticotrophin releasing factor, grooming and ingestive behavior. Life Sci. 1982 Oct 4;31(14):1459–1464. doi: 10.1016/0024-3205(82)90007-8. [DOI] [PubMed] [Google Scholar]
  25. Nicholson W. E., Davis D. R., Sherrell B. J., Orth D. N. Rapid radioimmunoassay for corticotropin in unextracted human plasma. Clin Chem. 1984 Feb;30(2):259–265. [PubMed] [Google Scholar]
  26. Orth D. N., Jackson R. V., DeCherney G. S., DeBold C. R., Alexander A. N., Island D. P., Rivier J., Rivier C., Spiess J., Vale W. Effect of synthetic ovine corticotropin-releasing factor. Dose response of plasma adrenocorticotropin and cortisol. J Clin Invest. 1983 Mar;71(3):587–595. doi: 10.1172/JCI110804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rivier C., Brownstein M., Spiess J., Rivier J., Vale W. In vivo corticotropin-releasing factor-induced secretion of adrenocorticotropin, beta-endorphin, and corticosterone. Endocrinology. 1982 Jan;110(1):272–278. doi: 10.1210/endo-110-1-272. [DOI] [PubMed] [Google Scholar]
  28. Rivier C., Rivier J., Vale W. Inhibition of adrenocorticotropic hormone secretion in the rat by immunoneutralization of corticotropin-releasing factor. Science. 1982 Oct 22;218(4570):377–379. doi: 10.1126/science.6289439. [DOI] [PubMed] [Google Scholar]
  29. Rivier C., Vale W. Modulation of stress-induced ACTH release by corticotropin-releasing factor, catecholamines and vasopressin. Nature. 1983 Sep 22;305(5932):325–327. doi: 10.1038/305325a0. [DOI] [PubMed] [Google Scholar]
  30. SAFFRAN M., SCHALLY A. V. The release of corticotrophin by anterior pituitary tissue in vitro. Can J Biochem Physiol. 1955 May;33(3):408–415. [PubMed] [Google Scholar]
  31. Saavedra J. M. Changes in dopamine, noradrenaline and adrenaline in specific septal and preoptic nuclei after acute immobilization stress. Neuroendocrinology. 1982 Nov;35(5):396–401. doi: 10.1159/000123413. [DOI] [PubMed] [Google Scholar]
  32. Sirinathsinghji D. J., Rees L. H., Rivier J., Vale W. Corticotropin-releasing factor is a potent inhibitor of sexual receptivity in the female rat. Nature. 1983 Sep 15;305(5931):232–235. doi: 10.1038/305232a0. [DOI] [PubMed] [Google Scholar]
  33. Spiess J., Rivier J., Rivier C., Vale W. Primary structure of corticotropin-releasing factor from ovine hypothalamus. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6517–6521. doi: 10.1073/pnas.78.10.6517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tilders F. J., Schipper J., Lowry P. J., Vermes I. Effect of hypothalamus lesions on the presence of CRF-immunoreactive nerve terminals in the median eminence and on the pituitary-adrenal response to stress. Regul Pept. 1982 Dec;5(1):77–84. doi: 10.1016/0167-0115(82)90077-5. [DOI] [PubMed] [Google Scholar]
  35. Vale W., Rivier C., Brown M. R., Spiess J., Koob G., Swanson L., Bilezikjian L., Bloom F., Rivier J. Chemical and biological characterization of corticotropin releasing factor. Recent Prog Horm Res. 1983;39:245–270. doi: 10.1016/b978-0-12-571139-5.50010-0. [DOI] [PubMed] [Google Scholar]
  36. Vale W., Spiess J., Rivier C., Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science. 1981 Sep 18;213(4514):1394–1397. doi: 10.1126/science.6267699. [DOI] [PubMed] [Google Scholar]
  37. Vellucci S. V. The effects of ether stress and betamethasone treatment on the concentrations of noradrenaline and dopamine in various regions of the rat brain. Br J Pharmacol. 1977 Aug;60(4):601–605. doi: 10.1111/j.1476-5381.1977.tb07541.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vernikos J., Dallman M. F., Bonner C., Katzen A., Shinsako J. Pituitary-adrenal function in rats chronically exposed to cold. Endocrinology. 1982 Feb;110(2):413–420. doi: 10.1210/endo-110-2-413. [DOI] [PubMed] [Google Scholar]
  39. Wehrenberg W. B., Brazeau P., Luben R., Böhlen P., Guillemin R. Inhibition of the pulsatile secretion of growth hormone by monoclonal antibodies to the hypothalamic growth hormone releasing factor (GRF). Endocrinology. 1982 Dec;111(6):2147–2148. doi: 10.1210/endo-111-6-2147. [DOI] [PubMed] [Google Scholar]
  40. Yasuda N., Greer M. A. Evidence that the hypothalamus mediates endotoxin stimulation of adrenocorticotropic hormone secretion. Endocrinology. 1978 Mar;102(3):947–953. doi: 10.1210/endo-102-3-947. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES