3 beta-hydroxysteroid dehydrogenase/isomerase and aromatase activity in primary cultures of developing zebra finch telencephalon: dehydroepiandrosterone as substrate for synthesis of androstenedione and estrogens.
3 beta-hydroxysteroid dehydrogenase/delta 5 - delta 4 isomerase (3 beta-HSD) activity was measured in primary dissociated cell cultures prepared from telencephalons of developing zebra finches. 3 beta-HSD activity was confirmed after cultures were incubated with [7-3H]pregnenolone (Preg) or (1,2,6,7-3H-) dehydroepiandrosterone (DHEA) and 3H-progesterone (Prog) and 3H-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 and 3H-estrone were also detected in the culture medium, presumably derived from the aromatization of 3H-AE or 3H-T produced from 3H-DHEA. To test this idea, cultures were incubated with 3H-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 of 3H-AE decreased in the media; in the presence of fadrozole, 3H-estrogens decreased but 3H-AE and its androgenic metabolite 3H-5 beta-androstanedione increased. These data demonstrate 3 beta-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.
Vanson
A
A
Department of Psychology, University of California, Los Angeles 90024, USA.
Arnold
A P
AP
Schlinger
B A
BA
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000735:Androstenedione / Q000096:biosynthesis*; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001717:Birds; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000096:biosynthesis*; D017316:Fadrozole / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D013997:Time Factors
D004965:Estrogen Antagonists; D004967:Estrogens; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D011284:Pregnenolone; D015096:3-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D017316:Fadrozole