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3β-Hydroxysteroid Dehydrogenase/Isomerase and Aromatase Activity in Primary Cultures of Developing Zebra Finch Telencephalon: Dehydroepiandrosterone as Substrate for Synthesis of Androstenedione and Estrogens
Authors:Ana Vanson  Arthur P Arnold  Barney A Schlinger
Institution:aDepartment of Psychology, University of California, Los Angeles, California, 90024;bDepartment of Physiological Science, Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, California, 90024
Abstract:3β-hydroxysteroid dehydrogenase/Δ5−Δ4isomerase (3β-HSD) activity was measured in primary dissociated cell cultures prepared from telencephalons of developing zebra finches. 3β-HSD activity was confirmed after cultures were incubated with 7-3H]pregneno- lone (Preg) or (1,2,6,7-3H-) dehydroepiandrosterone (DHEA) and3H-progesterone (Prog) and3H-androstenedione (AE) were detected in the medium. Product identity was confirmed by recrystallizations and by HPLC analysis. When DHEA was used as substrate,3H-estradiol and3H-estrone were also detected in the culture medium, presumably derived from the aromatization of3H-AE or3H-T produced from3H-DHEA. To test this idea, cultures were incubated with3H-DHEA together with radioinert AE or with fadrozole HCl, a potent and specific aromatase inhibitor. In the presence of radioinert AE,3H-AE increased but metabolites of3H-AE decreased in the media; in the presence of fadrozole,3H-estrogens decreased but3H-AE and its androgenic metabolite3H-5β-androstanedione increased. These data demonstrate 3β-HSD activity in the songbird brain. The presence of Prog and estradiol in these cultures suggest that Preg and DHEA can potentially serve as substrates for the ultimate formation of active sex steroids in the songbird telencephalon.
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