11β-HSD Types 1 and 2 in the Songbird Brain

Abstract

Glucocorticoid (GC) hormones act on the brain to regulate diverse functions, from behavior and homeostasis to the activity of the hypothalamic-pituitary-adrenal axis. Local regeneration and metabolism of GCs can occur in target tissues through the actions of the 11β-hydroxysteroid dehydrogenases [11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and 11 beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2), respectively] to regulate access to GC receptors. Songbirds have become especially important model organisms for studies of stress hormone action; however, there has been little focus on neural GC metabolism. Therefore, we tested the hypothesis that 11β-HSD1 and 11β-HSD2 are expressed in GC-sensitive regions of the songbird brain. Localization of 11β-HSD expression in these regions could provide precise temporal and spatial control over GC actions. We quantified GC sensitivity in zebra finch (Taeniopygia guttata) brain by measuring glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) expression across six regions, followed by quantification of 11β-HSD1 and 11β-HSD2 expression. We detected GR, MR, and 11β-HSD2 mRNA expression throughout the adult brain. Whereas 11β-HSD1 expression was undetectable in the adult brain, we detected low levels of expression in the brain of developing finches. Across several adult brain regions, expression of 11β-HSD2 covaried with GR and MR, with the exception of the cerebellum and hippocampus. It is possible that receptors in these latter two regions require direct access to systemic GC levels. Overall, these results suggest that 11β-HSD2 expression protects the adult songbird brain by rapid metabolism of GCs in a context and region-specific manner.

Keywords: 11 beta-hydroxysteroid dehydrogenase; glucocorticoid; mineralocorticoid; songbird; stress response.

Figure 1

Distribution of tissue collection times post-disturbance in adult male and female zebra finches. Males and females were sampled at similar times.

Figure 2

Quantitative PCR results showing mineralocorticoid receptor (MR) (top panel) and glucocorticoid receptor (GR) (bottom panel) expression patterns (relative to glyceraldehyde-3-phosphate dehydrogenase) across six brain regions in adult male (M) and female (F) zebra finches. Letters above bars represent significant differences. *Indicates a significant difference between males and females in CER. Bars are means ± 1 SE. Sample sizes are as follows (n = MR/GR): CER, cerebellum (17/16); DIEN, diencephalon (17/16); OT, optic tectum (17/17); NCM, caudomedial nidopallium (16/16); HP, hippocampus (17/17); cNp, caudal nidopallium (13/13).

Figure 3

Quantitative PCR results showing 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) (top panel) and 11 beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) (bottom panel) expression patterns (relative to glyceraldehyde-3-phosphate dehydrogenase) across six brain regions in adult male (M) and female (F) zebra finches. Letters above bars represent significant differences. Positive control tissues are presented for comparison (11β-HSD1: liver; 11β-HSD2: kidney). Bars are means ± 1 SE. Sample sizes are as follows (n = 11β-HSD2): CER, cerebellum (17); DIEN, diencephalon (17); OT, optic tectum (17); NCM, caudomedial nidopallium (16); HP, hippocampus (17); cNp, caudal nidopallium (13).

Figure 4

The relationship between average (±1 SE) MR and GR expression levels across six brain regions. Dashed line = best fit line with all six brain regions included. Solid line = best fit line when CER and HP were excluded from the analysis. Abbreviations: CER, cerebellum; DIEN, diencephalon; OT, optic tectum; NCM, caudomedial nidopallium; HP, hippocampus; cNp, caudal nidopallium.

Figure 5

The relationship between average (±1 SE) 11 beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and GR (left panel) and average 11β-HSD2 and MR (right panel) expression levels across six brain regions. Dashed line = best fit line with all six brain regions included. Solid line = best fit line when CER and HP were excluded from the analysis. Abbreviations: CER, cerebellum; DIEN, diencephalon; OT, optic tectum; NCM, caudomedial nidopallium; HP, hippocampus; cNp, caudal nidopallium; MR, mineralocorticoid receptor; GR, glucocorticoid receptor.