Regulation of aromatase, 5α‐ and 5β‐reductase in primary cell cultures of developing zebra finch telencephalon

Sex steroids act on the developing and adult telencephalon of songbirds to organize and activate the neural circuits required for the learning and production of song. Presumably, the availability of active androgens and estrogens to steroid‐sensitive neural circuits controlling song is modulated by the local expression of androgen‐metabolizing enzymes. Two enzymes, 5α‐ and 5β‐reductase, are expressed widely in the songbird telencephalon, as they are in the telencephalons of other avian species. These enzymes convert circulating testosterone (T) into the active and inactive metabolites, 5α‐ and 5β‐dihydrotestosterone (DHT), respectively. A third enzyme, aromatase, converts T into estradiol (E2) and is expressed at unusually high levels in several regions of the songbird telencephalon. In many tissues, including the brain, the regulation of expression of one or more of these enzymes can be a critical feature of their ability to control the production of active sex steroids. We have used primary cell cultures to examine factors that might regulate the expression of these enzymes in developing zebra finch telencephalon. Cultures were treated for 0‐72 h with sex steroids (T, E2, 5α‐DHT, and 5β‐DHT) or with dibutyryl cAMP. Afterward, activities of aromatase, 5α‐, and 5β‐reductase were determined or total RNA was extracted for Northern analysis. Treatments with cAMP increased both aromatase activity and aromatase mRNA levels by 220%. E2 significantly reduced aromatase activity by an average of 65%, whereas 5α‐ and 5β‐DHT had no effect on aromatase activity. Compared to untreated controls, E2 treatment decreased aromatase mRNA levels by 56%. None of these treatments consistently affected either 5α‐ or 5β‐reductase activities. These results suggest that telencephalic E2 may regulate its own synthesis by repression of aromatase expression, whereas factors that upregulate cAMP in the telencephalon can increase the local concentrations of E2. © 1998 John Wiley & Sons, Inc. J Neurobiol 36: 30–40, 1998