5 beta-reductase and other androgen-metabolizing enzymes in primary cultures of developing zebra finch telencephalon.
Enzymes in the avian brain irreversibly catalyze the conversion of androgens into either active metabolites (aromatase and 5 alpha-reductase) or inactive metabolites (5 beta-reductase), 5 beta-reductase is thought to influence the formation of active metabolites by reducing the concentration of androgenic substrate available for these reactions. However, because these enzymes have different regional, cellular and subcellular distributions in brain, the traditional method to measure enzyme activity in brain homogenates may be inaccurate because of artificial mixing of enzymes. Recently, we have prepared primary cell cultures from the telencephalons of developing zebra finches. Cell cultures offer the advantage that enzyme activity can be measured in live cells in which the relative distribution of enzymes may more closely reflect that found in vivo. We have previously reported that aromatase is expressed at high levels in these cultures, and that it is active in both neurons and in glia. Here we report on the activities of 5 alpha- and 5 beta-reductase in these cell cultures. Along with aromatase, 5 beta-reductase was expressed at high levels in these mixed cell cultures, including cultures highly enriched in glia. This suggests that 5 beta-reductase is present in non-neuronal cells in brain, possibly co-localized with aromatase. However, despite the presence of 5 beta-reductase, aromatase was detected reliably in vitro even when the concentration of substrate was low. Thus, 5 beta-reductase does not prevent the synthesis of estrogen in the telencephalon of developing zebra finches. By contrast, 5 alpha-reductase activity was very low or absent in these cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Schlinger
B A
BA
Department of Physiological Science, University of California, Los Angeles 90024, USA.
Amur-Umarjee
S
S
Campagnoni
A T
AT
Arnold
A P
AP
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001717:Birds / Q000378:metabolism*; D042944:Cholestenone 5 alpha-Reductase; D005260:Female; D007700:Kinetics; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D013687:Telencephalon / Q000378:metabolism*
D000728:Androgens; D010088:Oxidoreductases; D001141:Aromatase; D042944:Cholestenone 5 alpha-Reductase; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase