Tissue specific expression of 11BHSD and its effects on plasma corticosterone during the stress response

Perez, J. H., Swanson, R. E., Lau, H. J., Cheah, J., Bishop, V. R., Snell, K. R.S., Reid, A. M.A., Meddle, S. L., Wingfield, J. C. and Krause, J. S. (2020) Tissue specific expression of 11BHSD and its effects on plasma corticosterone during the stress response. Journal of Experimental Biology, 223, jeb.209346. (doi: 10.1242/jeb.209346) (PMID:31796607)

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is under complex regulatory control at multiple levels. Enzymatic regulation plays an important role in both circulating levels and target tissue exposure. Three key enzyme pathways are responsible for the immediate control of glucocorticoids. De novo synthesis of glucocorticoid from cholesterol involves a multistep enzymatic cascade. This cascade terminates with 11β-hydroxylase, responsible for the final conversion of 11 deoxy- precursors into active glucocorticoids. Additionally, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) controls regeneration of glucocorticoids from inactive metabolites, providing a secondary source of active glucocorticoids. Localized inactivation of glucocorticoids is under the control of Type 2 11β-HSD (11β-HSD2). The function of these enzymes is largely unexplored in wild species, particularly songbirds. Here we aim to explore the contribution of both clearance and generation of glucocorticoids to regulation of the hormonal stress response via use of pharmacological antagonists. Additionally, we mapped 11β-HSD gene expression. We found 11β-HSD1 primarily in liver, kidney, and adrenal glands though it was detectable across all tissue types. 11β-HSD2 was predominately expressed in the adrenal glands and kidney with moderate gonadal and liver expression. Inhibition of glucocorticoid generation by metyrapone was found to decrease levels peripherally, while both peripheral and central DETC administration resulted in elevated concentrations of corticosterone. These data suggest that during the stress response, peripheral antagonism of the 11β-HSD system has a greater impact on circulating glucocorticoid levels than central control. Further studies show aim to elucidate the respective roles of the 11β-HSD and 11β-hydroxylase enzymes.

• Item Type: Articles
• Additional Information: This work was supported by the National Science Foundation Division of Integrative Organismal Systems [IOS 1558049 to JCW] and Roslin Institute strategic grant funding from the Biotechnology and Biological Sciences Research Council [BB/P013759/1 to SLM]. J.C. Wingfield would like to acknowledge the University of California, Davis Endowed Chair in Physiology. The Danish Council for Independent Research supported the MATCH project [1323-00048B to KS] and Danish National Research Foundation supported Center for Macroecology, Evolution and Climate [DNRF96 to KS].
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Perez, Dr Jonathan
• Authors: Perez, J. H., Swanson, R. E., Lau, H. J., Cheah, J., Bishop, V. R., Snell, K. R.S., Reid, A. M.A., Meddle, S. L., Wingfield, J. C., and Krause, J. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Journal of Experimental Biology
• Publisher: Company of Biologists
• ISSN: 0022-0949
• ISSN (Online): 1477-9145
• Published Online: 03 December 2019
• Copyright Holders: Copyright © 2020. Published by The Company of Biologists Ltd
• First Published: First published in Journal of Experimental Biology
• Publisher Policy: Reproduced in accordance with the publisher copyright policy