Abstract
Dehydroepiandrosterone (DHEA) is a precursor to sex steroids such as androstenedione (AE), testosterone (T), and estrogens. DHEA has potent effects on brain and behavior, although the mechanisms remain unclear. One possible mechanism of action is that DHEA is converted within the brain to sex steroids. 3β-Hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) catalyzes the conversion of DHEA to AE. AE can then be converted to T and estrogen within the brain. We test the hypothesis that 3β-HSD is expressed in the adult brain in a region- and sex-specific manner using the zebra finch (Taeniopygia guttata), a songbird with robust sex differences in song behavior and telencephalic song nuclei. In zebra finch brain, DHEA is converted by 3β-HSD to AE and subsequently to estrogens and 5α- and 5β-reduced androgens. 3β-HSD activity is highest in the diencephalon and telencephalon. In animals killed within 2–3 min of disturbance, baseline 3β-HSD activity in portions of the telencephalon is higher in females than males. Acute restraint stress (10 min) decreases 3β-HSD activity in females but not in males, and in stressed animals, telencephalic 3β-HSD activity is greater in males than in females. Thus, the baseline sex difference is rapidly reversed by stress. To our knowledge, this is the first demonstration of 1) brain region differences in DHEA metabolism by 3β-HSD, 2) rapid modulation of 3β-HSD activity, and 3) sex differences in brain 3β-HSD and regulation by stress. Songbirds are good animal models for studying the regulation and functions of DHEA and neurosteroids in the nervous system.
Insight from animal models of environmentally driven epigenetic changes in the developing and adult brain
