11β-Hydroxysteroid dehydrogenase type 2 in zebrafish brain: a functional role in hypothalamus-pituitary-interrenal axis regulation
- Authors
- Alderman, S.L., and Vijayan, M.M.
- ID
- ZDB-PUB-121016-12
- Date
- 2012
- Source
- The Journal of endocrinology 215(3): 393-402 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- 11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics
- 11-beta-Hydroxysteroid Dehydrogenase Type 2/metabolism*
- Animals
- Glycyrrhetinic Acid/analogs & derivatives
- Glycyrrhetinic Acid/pharmacology
- Hydrocortisone/metabolism
- Hypothalamus/drug effects
- Hypothalamus/enzymology*
- Hypothalamus/metabolism*
- Pituitary Gland/drug effects
- Pituitary Gland/enzymology*
- Pituitary Gland/metabolism*
- Receptors, Mineralocorticoid/metabolism
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 23042946 Full text @ J. Endocrinol.
The type 2 11β-hydroxysteroid dehydrogenase (11βHSD2) converts active glucocorticoids to their inactive derivatives (ex. cortisol to cortisone). In most vertebrates, 11βHSD2 is essential for conferring aldosterone-specific actions in mineralocorticoid target tissues and for protecting glucocorticoid-sensitive tissues during stress. However, teleosts do not synthesize aldosterone, and the function of 11βHSD2 is poorly defined. The distribution of 11βHSD2 in non-mammalian brain is also largely unexplored. We tested the hypothesis that modulation of brain 11βHSD2 activity is involved in the stressor-mediated cortisol regulation in zebrafish (Danio rerio). In adult zebrafish, the stress effect on 11βHSD2 expression in the brain was tested using an acute air exposure followed by recovery over a 24 h period. 11βhsd2 transcripts were found in nearly all peripheral tissues examined, and a spatial map of its mRNA abundance in unstressed zebrafish brain revealed extensive distribution. Stressor exposure increased the conversion of 3H-cortisol to 3H-cortisone indicating enhanced 11βHSD2 activity in zebrafish brain. Promoter analysis of zebrafish 11βhsd2 gene revealed putative sites for cortisol-mediated transcriptional regulation of this gene. Furthermore, inhibition of 11βHSD2 activity by 18β-glycyrrhetinic acid resulted in elevated whole body cortisol levels and preoptic area mRNA abundance of corticotropin-releasing factor and mineralocorticoid receptor. Taken together, our results underscore an important role for brain 11βHSD2 involvement in the negative feedback regulation of cortisol post-stress in zebrafish.