Endocrinology, Vol 134, 1286-1296, Copyright © 1994 by Endocrine Society

ARTICLES

Roles of type I and II corticosteroid receptors in regulation of basal activity in the hypothalamo-pituitary-adrenal axis during the diurnal trough and the peak: evidence for a nonadditive effect of combined receptor occupation

MJ Bradbury, SF Akana and MF Dallman
Department of Physiology, University of California, San Francisco 94143- 0444.

Negative feedback regulation of basal activity in the hypothalamo- pituitary-adrenal (HPA) axis requires less corticosterone (B) at the trough (morning) than at the peak (evening) of the diurnal rhythm. It has been hypothesized that in the morning in rats, occupation of the high affinity, type I corticosteroid receptors is sufficient to inhibit adrenalectomy (ADX)-induced increases in plasma ACTH secretion, whereas in the evening, regulation occurs through the occupation of the lower affinity type II corticosteroid receptors. To examine this hypothesis, the sensitivity of ACTH to inhibition by two different doses of B or of dexamethasone (DEX) were compared in ADX rats killed in the morning or the evening (B has a higher affinity for type I receptors in vitro and in vivo; in vivo, DEX has a higher affinity for type II receptors). The requirement for greater concentrations of corticosteroids to inhibit ACTH secretion in the evening was verified. The effect of these treatments on the number of neurons immunoreactive for vasopressin (AVP) and on the expression of AVP messenger RNA (mRNA) in the parvocellular portion of the paraventricular nuclei was also examined. In the morning, plasma concentrations of B equivalent to the IC50 for the reduction of plasma ACTH in the morning reduced the amount of AVP mRNA, but not immunoreactive AVP cell number as compared with ADX rats. DEX reduced plasma ACTH in the morning but did not prevent high levels of expression of AVP mRNA or protein. AVP mRNA was more sensitive to B in the morning than in the evening. Antagonist to the type I receptor (spironolactone) given chronically to ADX rats treated with B increased plasma ACTH secretion at both times of day, even though the plasma B concentrations suggested occupancy of a large proportion of the type II receptors. To test the hypothesis that an interaction between the type I and II receptor is necessary for the control of HPA activity at the peak of the diurnal rhythm, ADX rats were given B or DEX, alone or in combination. DEX reduced evening plasma ACTH only in the presence of very low concentrations of B, suggesting that for full potency, type II receptor occupation requires type I receptor occupation. In summary, these results demonstrate that occupation of type I corticosteroid receptors is capable of controlling basal activity in the HPA axis in the morning and that in the evening, type I receptor occupation potentiates the inhibition of plasma ACTH by occupation of type II receptors.

This article has been cited by other articles:

				F. Spiga, L. R Harrison, S. A Wood, C. P MacSweeney, F. J Thomson, M. Craighead, M. Grassie, and S. L Lightman Effect of the glucocorticoid receptor antagonist Org 34850 on fast and delayed feedback of corticosterone release J. Endocrinol., February 1, 2008; 196(2): 323 - 330. [Abstract] [Full Text] [PDF]

				A. M. Rozeboom, H. Akil, and A. F. Seasholtz Mineralocorticoid receptor overexpression in forebrain decreases anxiety-like behavior and alters the stress response in mice PNAS, March 13, 2007; 104(11): 4688 - 4693. [Abstract] [Full Text] [PDF]

				A. Jaferi and S. Bhatnagar Corticosterone Can Act at the Posterior Paraventricular Thalamus to Inhibit Hypothalamic-Pituitary-Adrenal Activity in Animals that Habituate to Repeated Stress Endocrinology, October 1, 2006; 147(10): 4917 - 4930. [Abstract] [Full Text] [PDF]

				J. A. Shoener, R. Baig, and K. C. Page Prenatal exposure to dexamethasone alters hippocampal drive on hypothalamic-pituitary-adrenal axis activity in adult male rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1366 - R1373. [Abstract] [Full Text] [PDF]

				A. G. Bechtold and D. A. Scheuer Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R1003 - R1011. [Abstract] [Full Text] [PDF]

				T. W. W. Pace and R. L. Spencer Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1082 - E1088. [Abstract] [Full Text] [PDF]

				T. M. Buckley and A. F. Schatzberg Aging and the Role of the HPA Axis and Rhythm in Sleep and Memory-Consolidation Am J Geriatr Psychiatry, May 1, 2005; 13(5): 344 - 352. [Abstract] [Full Text] [PDF]

				S. E. la Fleur, S. F. Akana, S. L. Manalo, and M. F. Dallman Interaction between Corticosterone and Insulin in Obesity: Regulation of Lard Intake and Fat Stores Endocrinology, May 1, 2004; 145(5): 2174 - 2185. [Abstract] [Full Text] [PDF]

				C. Mattsson, M. Lai, J. Noble, E. McKinney, J. L. Yau, J. R. Seckl, and B. R. Walker Obese Zucker Rats Have Reduced Mineralocorticoid Receptor and 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression in Hippocampus--Implications for Dysregulation of the Hypothalamic-Pituitary-Adrenal Axis in Obesity Endocrinology, July 1, 2003; 144(7): 2997 - 3003. [Abstract] [Full Text] [PDF]

				E. A. Young, J. F. Lopez, V. Murphy-Weinberg, S. J. Watson, and H. Akil Mineralocorticoid Receptor Function in Major Depression Arch Gen Psychiatry, January 1, 2003; 60(1): 24 - 28. [Abstract] [Full Text] [PDF]

				M. Keller-Wood and C. E. Wood Pregnancy alters cortisol feedback inhibition of stimulated ACTH: studies in adrenalectomized ewes Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2001; 280(6): R1790 - R1798. [Abstract] [Full Text] [PDF]

				K. J. Kovacs, A. Foldes, and P. E. Sawchenko Glucocorticoid Negative Feedback Selectively Targets Vasopressin Transcription in Parvocellular Neurosecretory Neurons J. Neurosci., May 15, 2000; 20(10): 3843 - 3852. [Abstract] [Full Text] [PDF]

				T. Tajima, X.-M. Ma, S. R. Bornstein, and G. Aguilera Prenatal Dexamethasone Treatment Does Not Prevent Alterations of the Hypothalamic Pituitary Adrenal Axis in Steroid 21-Hydroxylase Deficient Mice Endocrinology, July 1, 1999; 140(7): 3354 - 3362. [Abstract] [Full Text]

				E. A. Young, J. F. Lopez, V. Murphy-Weinberg, S. J. Watson, and H. Akil The Role of Mineralocorticoid Receptors in Hypothalamic-Pituitary-Adrenal Axis Regulation in Humans J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3339 - 3345. [Abstract] [Full Text]

				E. R. de Kloet, E. Vreugdenhil, M. S. Oitzl, and M. Joëls Brain Corticosteroid Receptor Balance in Health and Disease Endocr. Rev., June 1, 1998; 19(3): 269 - 301. [Abstract] [Full Text]

				R. L. Spencer, P. J. Kim, B. A. Kalman, and M. A. Cole Evidence for Mineralocorticoid Receptor Facilitation of Glucocorticoid Receptor-Dependent Regulation of Hypothalamic-Pituitary-Adrenal Axis Activity Endocrinology, June 1, 1998; 139(6): 2718 - 2726. [Abstract] [Full Text] [PDF]

				I. Dijkstra, F. J. H. Tilders, G. Aguilera, A. Kiss, C. Rabadan-Diehl, N. Barden, S. Karanth, F. Holsboer, and J. M. H. M. Reul Reduced Activity of Hypothalamic Corticotropin-Releasing Hormone Neurons in Transgenic Mice with Impaired Glucocorticoid Receptor Function J. Neurosci., May 15, 1998; 18(10): 3909 - 3918. [Abstract] [Full Text] [PDF]

				E. A. Galliven, A. Singh, D. Michelson, S. Bina, P. W. Gold, and P. A. Deuster Hormonal and metabolic responses to exercise across time of day and menstrual cycle phase J Appl Physiol, December 1, 1997; 83(6): 1822 - 1831. [Abstract] [Full Text] [PDF]

				B. M. Tannenbaum, D. N. Brindley, G. S. Tannenbaum, M. F. Dallman, M. D. McArthur, and M. J. Meaney High-fat feeding alters both basal and stress-induced hypothalamic-pituitary-adrenal activity in the rat Am J Physiol Endocrinol Metab, December 1, 1997; 273(6): E1168 - E1177. [Abstract] [Full Text] [PDF]

				S. F. Akana and M. F. Dallman Chronic Cold in Adrenalectomized, Corticosterone (B)-Treated Rats: Facilitated Corticotropin Responses to Acute Restraint Emerge as B Increases Endocrinology, August 1, 1997; 138(8): 3249 - 3258. [Abstract] [Full Text] [PDF]

				J. S. Petrides, P. W. Gold, G. P. Mueller, A. Singh, C. Stratakis, G. P. Chrousos, and P. A. Deuster Marked differences in functioning of the hypothalamicpituitary-adrenal axis between groups of men J Appl Physiol, June 1, 1997; 82(6): 1979 - 1988. [Abstract] [Full Text] [PDF]