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.
Highlights
Glucocorticoid (GC) hormones regulate numerous biological processes, including crucial actions on the central nervous system such as feedback regulation of adrenal function, activation or suppression of cognitive and locomotor activity, and regulation of feeding behaviors [1]
Sensitivity to GC effects is mediated through the intracellular mineralocorticoid receptor (MR) and glucocorticoid receptor (GR); acute stress-induced effects are mediated by the lower-affinity GR, while the high-affinity MR mediates baseline and early stress-induced effects [1, 9]
Glucocorticoid receptor expression levels differed between brain regions (F5,82 = 191.5; P < 0.001) with highest levels in CER, followed by NCM and caudal nidopallium (cNp), and lowest levels in DIEN, OT, and HP (Figure 2)
Summary
Glucocorticoid (GC) hormones regulate numerous biological processes, including crucial actions on the central nervous system such as feedback regulation of adrenal function, activation or suppression of cognitive and locomotor activity, and regulation of feeding behaviors [1]. We confirmed expression of 11β-HSD2 in two regions of the adult zebra finch (Taeniopygia guttata) brain, the caudal nidopallium (cNp) and hippocampus (HP). To enable a direct comparison of expression across ages, the remaining caudal TEL from four of the adults utilized in the main study above was processed in parallel with these developing finch samples. The supernatant was decanted and incubated at room temperature for 5 min, and Figure 1 | Distribution of tissue collection times post-disturbance in adult male and female zebra finches. Tubes were briefly vortexed, incubated at room temperature for 10 min, centrifuged at 12,000 g for 10 min, and the supernatant removed, leaving the RNA pellet in place. We included positive control tissue in the adult 11β-HSD2 standard curves, pooling all brain regions together with a small amount of kidney cDNA. All standard curves utilized a fourfold dilution with curves extending from 1:1 to 1:256 for GR, MR, and GAPDH, and standard curves ranging from 1:1 to 1:1,024 (11β-HSD1) or 1:4,096 (11β-HSD2)
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