This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanimura, S. M. Articles by Watts, A. G. Search for Related Content PubMed PubMed Citation Articles by Tanimura, S. M. Articles by Watts, A. G.

Corticosterone Can Facilitate as Well as Inhibit Corticotropin-Releasing Hormone Gene Expression in the Rat Hypothalamic Paraventricular Nucleus¹

Program in Neural, Informational, and Behavioral Sciences, and Neuroscience Graduate Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-2520

Address all correspondence and requests for reprints to: Alan G. Watts, D. Phil, Department of Biological Sciences, Hedco Neuroscience Building, MC 2520, University of Southern California, Los Angeles, California 90089-2520. E-mail: watts{at}rcf.usc.edu

We have used in situ hybridization to investigate how basal levels of circulating corticosterone modulate CRH gene transcription in the neuroendocrine parvicellular part of the hypothalamic paraventricular nucleus (PVHmpd) during sustained hypovolemia. In the absence of the stressor, the accumulation rate of the CRH primary transcript exhibited a dose dependency on low maintained levels of plasma corticosterone similar to that previously reported for the mature messenger RNA (mRNA); levels declined as plasma corticosterone increased. In response to hypovolemia, the absence of corticosterone compromised CRH gene transcription mechanisms to mount the activated response seen in intact animals. However, adrenalectomized rats with low doses of corticosterone (insufficient to normalize thymus weights) showed an augmented mRNA response compared with that in intact animals. When replaced corticosterone normalized thymus weights, the magnitude of the mRNA response was reduced to that seen in intact animals. In contrast to CRH gene regulation, PVHmpd proenkephalin mRNA levels were unaffected by corticosterone concentrations. These results suggest that corticosterone affects CRH gene transcription in the PVHmpd using two mechanisms: first, inhibition, which probably uses type II glucocorticoid receptor-dependent mechanisms and contributes to classic negative feedback; and second, facilitation, which is seen at low plasma concentrations and maintains gene transcription in the presence of sustained stress, possibly using type I mechanisms. This suggests that one reason why adrenal insufficiency severely compromises survival of sustained stress is that CRH gene transcription cannot be maintained without previous exposure to low levels of plasma corticosterone.

This article has been cited by other articles:

				N. Marissal-Arvy, A. Gaumont, A. Langlois, F. Dabertrand, M. Bouchecareilh, C. Tridon, and P. Mormede Strain differences in hypothalamic pituitary adrenocortical axis function and adipogenic effects of corticosterone in rats J. Endocrinol., December 1, 2007; 195(3): 473 - 484. [Abstract] [Full Text] [PDF]

				L. M. Gorton, A. M. Khan, M. Bohland, G. Sanchez-Watts, C. M. Donovan, and A. G. Watts A Role for the Forebrain in Mediating Time-of-Day Differences in Glucocorticoid Counterregulatory Responses to Hypoglycemia in Rats Endocrinology, December 1, 2007; 148(12): 6026 - 6039. [Abstract] [Full Text] [PDF]

				K. Mukherjee, A. Knisely, and L. Jacobson Partial Glucocorticoid Agonist-Like Effects of Imipramine on Hypothalamic-Pituitary-Adrenocortical Activity, Thymus Weight, and Hippocampal Glucocorticoid Receptors in Male C57BL/6 Mice Endocrinology, September 1, 2004; 145(9): 4185 - 4191. [Abstract] [Full Text] [PDF]

				V. Prima, M. Tennant, O. S. Gorbatyuk, N. Muzyczka, P. J. Scarpace, and S. Zolotukhin Differential Modulation of Energy Balance by Leptin, Ciliary Neurotrophic Factor, and Leukemia Inhibitory Factor Gene Delivery: Microarray Deoxyribonucleic Acid-Chip Analysis of Gene Expression Endocrinology, April 1, 2004; 145(4): 2035 - 2045. [Abstract] [Full Text] [PDF]

				A. G. Watts, S. Tanimura, and G. Sanchez-Watts Corticotropin-Releasing Hormone and Arginine Vasopressin Gene Transcription in the Hypothalamic Paraventricular Nucleus of Unstressed Rats: Daily Rhythms and Their Interactions with Corticosterone Endocrinology, February 1, 2004; 145(2): 529 - 540. [Abstract] [Full Text] [PDF]

				A. M. Khan and A. G. Watts Intravenous 2-Deoxy-D-Glucose Injection Rapidly Elevates Levels of the Phosphorylated Forms of p44/42 Mitogen-Activated Protein Kinases (Extracellularly Regulated Kinases 1/2) in Rat Hypothalamic Parvicellular Paraventricular Neurons Endocrinology, January 1, 2004; 145(1): 351 - 359. [Abstract] [Full Text] [PDF]

				K. D. Laugero, F. Gomez, S. Manalo, and M. F. Dallman Corticosterone Infused Intracerebroventricularly Inhibits Energy Storage and Stimulates the Hypothalamo-Pituitary Axis in Adrenalectomized Rats Drinking Sucrose Endocrinology, December 1, 2002; 143(12): 4552 - 4562. [Abstract] [Full Text] [PDF]

				A. G. Watts and G. Sanchez-Watts Interactions between Heterotypic Stressors and Corticosterone Reveal Integrative Mechanisms for Controlling Corticotropin-Releasing Hormone Gene Expression in the Rat Paraventricular Nucleus J. Neurosci., July 15, 2002; 22(14): 6282 - 6289. [Abstract] [Full Text] [PDF]

				V. Chesnokova and S. Melmed Leukemia Inhibitory Factor Mediates the Hypothalamic Pituitary Adrenal Axis Response to Inflammation Endocrinology, November 1, 2000; 141(11): 4032 - 4040. [Abstract] [Full Text] [PDF]

				R. Andres, O. Marti, and A. Armario Direct evidence of acute stress-induced facilitation of ACTH response to subsequent stress in rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1999; 277(3): R863 - R868. [Abstract] [Full Text] [PDF]

				O. Marti, R. Andres, and A. Armario Defective ACTH response to stress in previously stressed rats: dependence on glucocorticoid status Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1999; 277(3): R869 - R877. [Abstract] [Full Text] [PDF]

				A. G. Watts, G. Sanchez-Watts, and A. B. Kelly Distinct Patterns of Neuropeptide Gene Expression in the Lateral Hypothalamic Area and Arcuate Nucleus Are Associated with Dehydration-Induced Anorexia J. Neurosci., July 15, 1999; 19(14): 6111 - 6121. [Abstract] [Full Text] [PDF]

				S. M. Tanimura, G. Sanchez-Watts, and A. G. Watts Peptide Gene Activation, Secretion, and Steroid Feedback during Stimulation of Rat Neuroendocrine Corticotropin-Releasing Hormone Neurons Endocrinology, September 1, 1998; 139(9): 3822 - 3829. [Abstract] [Full Text] [PDF]