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

Department of Physiological Science and Laboratory of Neuroendocrinology of the Brain Research Institute (K.K.S., N.A.A., B.A.S.), University of California, Los Angeles, Los Angeles, California 90095; and Department of Ecology and Evolutionary Biology (M.H.), Princeton University, Princeton, New Jersey 08544

Address all correspondence and requests for reprints to: Kiran Soma, Department of Physiological Science, P.O. Box 951527, University of California, Los Angeles, Los Angeles, California 90095-1527. E-mail: kiran{at}physci.ucla.edu.

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. 3ß-Hydroxysteroid dehydrogenase/5-4 isomerase (3ß-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 3ß-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 3ß-HSD to AE and subsequently to estrogens and 5- and 5ß-reduced androgens. 3ß-HSD activity is highest in the diencephalon and telencephalon. In animals killed within 2–3 min of disturbance, baseline 3ß-HSD activity in portions of the telencephalon is higher in females than males. Acute restraint stress (10 min) decreases 3ß-HSD activity in females but not in males, and in stressed animals, telencephalic 3ß-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 3ß-HSD, 2) rapid modulation of 3ß-HSD activity, and 3) sex differences in brain 3ß-HSD and regulation by stress. Songbirds are good animal models for studying the regulation and functions of DHEA and neurosteroids in the nervous system.

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