3β-Hydroxysteroid Dehydrogenase/Isomerase and Aromatase Activity in Primary Cultures of Developing Zebra Finch Telencephalon: Dehydroepiandrosterone as Substrate for Synthesis of Androstenedione and Estrogens

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.     

Inherited Neurodegenerative Disorders Caused by CAG/Polyglutamine Tract Expansions: Symposium Introduction

At the beginning of this decade, the American Association of Neurology decided that the 1990's should be labelled "the decade of the brain" for expected advances in our understanding of neurological disorders and neuroscience. By the end of this decade, clinicians and researchers who work in the field of inherited neurological disorders might well remember the 1990's as "the decade of the trinucleotide repeat". At the time of writing this introduction, eleven inherited neurological disorders have been found to be caused by expansions of trinucleotide repeats, and a twelfth trinucleotide repeat expansion mutation has been identified (6), although the gene containing this mutant triplet repeat has not been cloned to our knowledge (Table 1).