Endocrinology, Vol 123, 396-405, Copyright © 1988 by Endocrine Society

ARTICLES

Corticotropin-releasing factor receptors and pituitary adrenal responses during immobilization stress

RL Hauger, MA Millan, M Lorang, JP Harwood and G Aguilera
Veterans Administration Medical Center, La Jolla, California 92103.

The regulation of pituitary and brain CRF receptors and corticotroph responses during stress were studied in rats subjected to prolonged immobilization. Plasma ACTH levels showed the characteristic biphasic changes, with a rapid 23-fold increase in 15 min, followed by a decrease to about twice the basal levels after 6-h immobilization. In contrast, plasma corticosterone levels were markedly elevated throughout the duration of the stress. Pituitary CRF receptor content, measured by binding of [125I]Tyr-ovine CRF to pituitary membrane-rich fractions, was unchanged after 2.5 h, but was reduced by 28 +/- 2.7% (+/- SE) and 47.6 +/- 1.1% after 18 and 48 h of immobilization, respectively. These results were confirmed by autoradiography in slide- mounted frozen pituitary sections. In contrast, no changes in CRF receptor content were observed in brain areas, including olfactory bulb, frontoparietal cortex, hippocampus, amygdala, and lateral septum. A concomitant decrease in immunoreactive (ir) CRF content in the median eminence of rats immobilized for 48 h is consistent with the hypothesis that increased release of CRF into the portal circulation occurs during chronic stress. Despite pituitary CRF receptor loss and reduced in vitro responses to CRF, the increases in plasma ACTH and corticosterone in vivo after ether exposure or CRF injection were greater and more prolonged in rats immobilized for 48 h than in nonimmobilized controls. The decrease in pituitary CRF receptors was accompanied by decreased CRF-stimulated cAMP and ACTH release in cultured pituitary cells from 48-h restrained rats. However, concomitant incubation of cells with CRF and vasopressin restored cAMP and ACTH responses to control levels, suggesting that the simultaneous release of both regulators from the hypothalamus determines the plasma ACTH level. These findings indicate that the decrease in plasma ACTH during the adaptation phase to stress is accompanied by decreases in pituitary CRF receptors. However, the enhanced pituitary response to a superimposed stress or CRF injection implies that the decrease in plasma ACTH levels during prolonged stress may be due to adaptive changes at the central level. These findings emphasize the importance of the integrated actions of CRF and other regulators in the control of the pituitary adrenal-axis during stress.

This article has been cited by other articles:

				G. Yu, H. Chen, W. Zhao, S. G. Matta, and B. M. Sharp Nicotine Self-Administration Differentially Regulates Hypothalamic Corticotropin-Releasing Factor and Arginine Vasopressin mRNAs and Facilitates Stress-Induced Neuronal Activation J. Neurosci., March 12, 2008; 28(11): 2773 - 2782. [Abstract] [Full Text] [PDF]

				D. C. Choi, N. K. Evanson, A. R. Furay, Y. M. Ulrich-Lai, M. M. Ostrander, and J. P. Herman The Anteroventral Bed Nucleus of the Stria Terminalis Differentially Regulates Hypothalamic-Pituitary-Adrenocortical Axis Responses to Acute and Chronic Stress Endocrinology, February 1, 2008; 149(2): 818 - 826. [Abstract] [Full Text] [PDF]

				J. A. CHESTER, G. DE PAULA BARRENHA, A. DEMARIA, and A. FINEGAN DIFFERENT EFFECTS OF STRESS ON ALCOHOL DRINKING BEHAVIOUR IN MALE AND FEMALE MICE SELECTIVELY BRED FOR HIGH ALCOHOL PREFERENCE Alcohol Alcohol., January 1, 2006; 41(1): 44 - 53. [Abstract] [Full Text] [PDF]

				C. A. Roca, P. J. Schmidt, M. Altemus, P. Deuster, M. A. Danaceau, K. Putnam, and D. R. Rubinow Differential Menstrual Cycle Regulation of Hypothalamic-Pituitary-Adrenal Axis in Women with Premenstrual Syndrome and Controls J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3057 - 3063. [Abstract] [Full Text] [PDF]

				K. Pacak and M. Palkovits Stressor Specificity of Central Neuroendocrine Responses: Implications for Stress-Related Disorders Endocr. Rev., August 1, 2001; 22(4): 502 - 548. [Abstract] [Full Text] [PDF]

				L. Arborelius, K. H. Skelton, K. V. Thrivikraman, P. M. Plotsky, D. W. Schulz, and M. J. Owens Chronic Administration of the Selective Corticotropin-Releasing Factor 1 Receptor Antagonist CP-154,526: Behavioral, Endocrine and Neurochemical Effects in the Rat J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 588 - 597. [Abstract] [Full Text]

				B. Bonaz and S. Rivest Effect of a chronic stress on CRF neuronal activity and expression of its type 1 receptor in the rat brain Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1998; 275(5): R1438 - R1449. [Abstract] [Full Text] [PDF]

				J. C. Day, M. Koehl, V. Deroche, M. Le Moal, and S. Maccari Prenatal Stress Enhances Stress- and Corticotropin-Releasing Factor-Induced Stimulation of Hippocampal Acetylcholine Release in Adult Rats J. Neurosci., March 1, 1998; 18(5): 1886 - 1892. [Abstract] [Full Text] [PDF]

				B. Yu and P. Shinnick-Gallagher Corticotropin-Releasing Factor Increases Dihydropyridine- and Neurotoxin-Resistant Calcium Currents in Neurons of the Central Amygdala J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 170 - 179. [Abstract] [Full Text]

				J. Raber, R. D. O'Shea, F. E. Bloom, and I. L. Campbell Modulation of Hypothalamic-Pituitary-Adrenal Function by Transgenic Expression of Interleukin-6 in the CNS of Mice J. Neurosci., December 15, 1997; 17(24): 9473 - 9480. [Abstract] [Full Text] [PDF]

				X.-M. Ma, A. Levy, and S. L. Lightman Emergence of an Isolated Arginine Vasopressin (AVP) Response to Stress after Repeated Restraint: A Study of Both AVP and Corticotropin-Releasing Hormone Messenger Ribonucleic Acid (RNA) and Heteronuclear RNA Endocrinology, October 1, 1997; 138(10): 4351 - 4357. [Abstract] [Full Text] [PDF]

				A. C. E. Linthorst, C. Flachskamm, S. J. Hopkins, M. E. Hoadley, MartaS. Labeur, F. Holsboer, and J. M. H. M. Reul Long-Term Intracerebroventricular Infusion of Corticotropin-Releasing Hormone Alters Neuroendocrine, Neurochemical, Autonomic, Behavioral, and Cytokine Responses to a Systemic Inflammatory Challenge J. Neurosci., June 1, 1997; 17(11): 4448 - 4460. [Abstract] [Full Text] [PDF]