Dehydroepiandrosterone Metabolism by 3 - Hydroxysteroid Dehydrogenase/ 5- 4 Isomerase in Adult Zebra Finch Brain: Sex Difference and Rapid Effect of Stress

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. 3 -Hydroxysteroid dehydrogenase/ 54 isomerase (3 -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 3 -HSD is expressed in the adult brain in a regionand 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 3 -HSD to AE and subsequently to estrogens and 5 and 5 -reduced androgens. 3 -HSD activity is highest in the diencephalon and telencephalon. In animals killed within 2–3 min of disturbance, baseline 3 -HSD activity in portions of the telencephalon is higher in females than males. Acute restraint stress (10 min) decreases 3 -HSD activity in females but not in males, and in stressed animals, telencephalic 3 -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 3 -HSD, 2) rapid modulation of 3 -HSD activity, and 3) sex differences in brain 3 -HSD and regulation by stress. Songbirds are good animal models for studying the regulation and functions of DHEA and neurosteroids in the nervous system. (Endocrinology 145: 1668–1677, 2004)