REGULATION OF AROMATASE, 5-ALPHA-REDUCTASE AND 5-BETA-REDUCTASE IN PRIMARY-CELL CULTURES OF DEVELOPING ZEBRA FINCH TELENCEPHALON

Sex steroids act on the developing and adult telencephalon of songbird s to organize and activate the neural circuits required for the learni ng and production of song. Presumably, the availability of active andr ogens and estrogens to steroid-sensitive neural circuits controlling s ong is modulated by the local expression of androgen-metabolizing enzy mes. Two enzymes, 5 alpha- and 5 beta-reductase, are expressed widely in the songbird telencephalon, as they are in the telencephalons of ot her avian species. These enzymes convert circulating testosterone (T) into the active and inactive metabolites, 5 alpha- and 5 beta-dihydrot estosterone (DHT), respectively. A third enzyme, aromatase, converts T into estradiol (E-2) and is expressed at unusually high levels in sev eral regions of the songbird telencephalon. In many tissues, including the brain, the regulation of expression of one or more of these enzym es can be a critical feature of their ability to control the productio n of active sex steroids. We have used primary cell cultures to examin e factors that might regulate the expression of these enzymes in devel oping zebra finch telencephalon. Cultures were treated for 0-72 h with sex steroids (T, E-2, 5 alpha-DHT, and 5 beta-DHT) or with dibutyryl cAMP. Afterward, activities of aromatase, 5 alpha-, and 5 beta-reducta se were determined or total RNA was extracted for Northern analysis. T reatments with cAMP increased both aromatase activity and aromatase mR NA levels by 220%. E-2 significantly reduced aromatase activity by an average of 65%, whereas 5 alpha- and 5 beta-DHT had no effect on aroma tase activity. Compared to untreated controls, E-2 treatment decreased aromatase mRNA levels by 56%. None of these treatments consistently a ffected either 5 alpha- or 5 beta-reductase activities. These results suggest that telencephalic E-2 may regulate its own synthesis by repre ssion of aromatase expression, whereas factors that upregulate cAMP in the telencephalon can increase the local concentrations of E-2. (C) 1 998 John Wiley & Sons, Inc.