11β-Hydroxysteroid dehydrogenase type 2 in zebrafish brain: a functional role in hypothalamus-pituitary-interrenal axis regulation

Abstract

The type 2, 11b-hydroxysteroid dehydrogenase (Hsd11b2) converts active glucocorticoids to their inactive derivatives (e.g. cortisol to cortisone). In most vertebrates, Hsd11b2 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 Hsd11b2 is poorly defined. The distribution of Hsd11b2 in nonmammalian brain is also largely unexplored. We tested the hypothesis that modulation of brain Hsd11b2 activity is involved in stressor-mediated cortisol regulation in zebrafish (Danio rerio). In adult zebrafish, the stress effect on Hsd11b2 expression in the brain was tested using acute air exposure followed by recovery over a 24-h period. hsd11b2 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 3 H-cortisol to 3 H-cortisone indicating enhanced Hsd11b2 activity in zebrafish brain. Promoter analysis of zebrafish hsd11b2 gene revealed putative sites for cortisol-mediated transcriptional regulation of this gene. Furthermore, inhibition of Hsd11b2 activity by 18b-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 Hsd11b2 involvement in the negative feedback regulation of cortisol poststress in zebrafish.

Effect of the liquorice root derivatives on salt and water balance in a teleost fish, rainbow trout (Oncorhynchus mykiss)

“…In this regard, the hypothesis that LRDs will alter gill ionoregulatory elements can be accepted, but in this study, these changes do not impact overall salt and water balance. The view that LRDs can alter cortisol metabolism is consistent with Alderman and Vijayan (2012) who showed that 18βGA decreased 11β-HSD2 activity and elevated whole body cortisol levels in zebrafish. The latter may have been influenced by LRD-induced corticosteroid-mediated events in ionoregulatory tissues of fishes in part due to changes in circulating cortisol levels.…”

“…Nevertheless, 18βGA has been reported to potentiate aldosterone-mediated active Na + transport (uptake) across frog skin (Ishikawa and Saito, 1980), and more recently Alderman and Vijayan (2012) have reported that in zebrafish 18βGA decreased brain 11β-HSD2 activity with an associated increase in whole body cortisol levels. This suggested that 11β-HSD2 can potentially affect the negative feedback loop of corticosteroid synthesis in zebrafish.…”

Stress in Atlantic salmon: response to unpredictable chronic stress

“…The lower 11βhsd2 transcript level may result in higher cortisol availability; we interpret these results combined as a search for a new balance in cortisol action under chronic stress conditions. Promotor analysis in zebrafish revealed putative sites for cortisol-mediated regulation of transcription of 11βhsd2 and (chemical) inhibition of 11βhsd2 activity resulted in increased POA crf expression and elevated cortisol levels (Alderman and Vijayan, 2012). Taken together, these findings indicate a pivotal role for 11βhsd2 in negative feedback control of the stress axis.…”

Maternal cortisol stimulates neurogenesis and affects larval behaviour in zebrafish

“…While the mechanism(s) is unclear, a recent study suggested a role for ATP-binding cassette transporters in the rapid cortisol clearance in threespine stickleback ( Gasterosteus aculeatus ) embryos40. Another possibility is the enzyme 11βHSD2, which converts cortisol to inactive cortisone and contains putative glucocorticoid response elements (GRE) in its promoter region41. This enzyme plays a role in countering exposure to cortisol excess in zebrafish ovarian follicles5, but its role in embryos remains to be elucidated.…”