11ß hydroxysteroid dehydrogenases regulate circulating glucocorticoids but not central gene expression.

Area of Science:

• Endocrinology
• Neurobiology
• Avian Physiology

Background:

• Glucocorticoids (GCs) are vital hormones regulating physiology and behavior.
• 11ß-hydroxysteroid dehydrogenases (11ß-HSD1 and 11ß-HSD2) control GC activity by regeneration and inactivation.
• Their roles in birds, particularly peripheral regulation of circulating GCs, remain poorly understood.

Purpose of the Study:

• To investigate the functional role of 11ß-HSD enzymes in regulating circulating GCs and central GC-dependent gene expression in adult zebra finches.
• To probe the effects of the 11ß-HSD inhibitor carbenoxolone (CBX) on GC dynamics.

Main Methods:

• Administration of carbenoxolone (CBX), an 11ß-HSD inhibitor, via peripheral injection in adult zebra finches.
• Measurement of circulating GCs at baseline and after CBX injection.
• Analysis of GC-dependent gene expression in micro-dissected brain regions following co-incubation with CBX and GCs.

Main Results:

• Peripheral CBX injection significantly increased baseline GCs, indicating a dominant role for 11ß-HSD2 in regulating circulating GCs.
• Central 11ß-HSD2, the only expressed isoform in the zebra finch brain, did not affect GC-dependent gene expression when inhibited.
• These findings suggest peripheral 11ß-HSD2 attenuates circulating GCs, while central 11ß-HSD2 may modulate local GC actions in the brain.

Conclusions:

• Peripheral 11ß-HSD2 plays a key role in controlling circulating glucocorticoid levels in songbirds.
• Central 11ß-HSD2's impact on gene expression is minimal, suggesting alternative regulatory functions like fine-tuning membrane GC actions.
• This study provides novel insights into glucocorticoid secretion and action dynamics in zebra finches.