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Endocrine Research Laboratory, Aurora St Lukes Medical Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53215, USA
1 Center for Neuropharmacology and Neurosciences, Albany Medical College, Albany, New York 12208, USA
(Requests for offprints should be addressed to H Raff who is now at Endocrinology, St Lukes Physicians Office Building, 2801 W. KK River Pky, Suite 245, Milwaukee, Wisconsin 53215, USA; Email: hraff{at}mcw.edu)
The objective of this study was to determine the effects of manipulating glucocorticoid negative feedback on acute ACTH and corticosterone responses to corticotropin-releasing hormone (CRH) injection in 7-day-old rats exposed to normoxia or hypoxia from birth. Chemical adrenalectomy was achieved with aminoglutethimide, and glucocorticoids were replaced with a low dose of dexamethasone. Hypoxia per se increased basal plasma corticosterone and attenuated the plasma ACTH response to CRH. Aminoglutethimide per se decreased plasma corticosterone and strongly increased basal plasma ACTH and anterior pituitary POMC gene expression. Dexamethasone partially attenuated elevations in basal plasma ACTH due to aminoglutethimide in both normoxic and hypoxic pups, but inhibited anterior pituitary POMC expression and CRH-induced plasma ACTH only in hypoxic pups. Despite this inhibition, hypoxic pups treated with both dexamethasone and aminoglutethimide still exhibited a significant CRH-induced increment in plasma ACTH, which was lacking in hypoxic pups not treated with either dexamethasone or aminoglutethimide. We conclude that ACTH responses to acute stimuli in hypoxic neonatal rats are prevented by ACTH-independent increases in corticosterone, rather than by intrinsic hypothalamicpituitary hypoactivity.
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E. D. Bruder, J. K. Taylor, K. J. Kamer, and H. Raff Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1195 - R1203. [Abstract] [Full Text] [PDF] |
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