EXPRESSION OF NEURAL 5-ALPHA-REDUCTASE MESSENGER-RIBONUCLEIC-ACID - COMPARISON TO 5-ALPHA-REDUCTASE ACTIVITY DURING PRENATAL DEVELOPMENT IN THE RAT

The present study was designed to characterize the developmental pattern of 5α-reductase messenger RNA (mRNA) levels and enzyme activity in intact medial basal hypothalamic (MBH) and preoptic area (POA) tissue fragments of rats during fetal development. 5α-Reductase activity was determined using [3H]testosterone as the substrate and quantifying, by TLC, the radiolabeled 5α-reduced metabolites (dihydrotestosterone [DHT] and 5α-androstane-3α, 17β-diol). Confirmation of the identity of the [3H]5α-DHT formed was demonstrated by recrystallization of the derivatized DHT to constant specific activity. Under saturating substrate conditions (1.7 µM testosterone), there were no significant sex differences (male vs. female) detected in neural 5α-reductase during prenatal, perinatal, or neonatal development. 5α-Reductase activity was low but detectable at gestational day (GD) 15 (≈10 pmol/h.mg protein), increased over 3-fold to peak levels at GD 18, and then declined to moderate levels at GD 22 (≈22 pmol/h.mg protein) and 4 days after birth (≈17 pmol/h.mg protein). In addition, the developmental pattern of 5α-reductase mRNA expression in fetal MBH-POA tissue was determined, by RNA blot hybridization, using a complementary DNA encoding the rat 5α-reductase enzyme. A single mRNA species was detected at 2.5 kilobase in MBH-POA tissue, which is similar in size to adult rat liver and prostate 5α-reductase mRNA. At GD 15, 5α-reductase mRNA was clearly detectable; the abundance increased on GD 17, remained at maximal levels at GDs 18, 19, and 20, and then decreased to moderate levels on GD 22. A correlation calculated between the normalized 5α-reductase mRNA levels and enzyme activities revealed a strong correspondence between mRNA abundance and enzyme activity values during prenatal development, r = 0.80, P = 0.056. These findings indicate that neural 5α-reductase activity may be developmentally regulated, and that the changes in 5α-reductase activity in MBH-POA tissue during late fetal development are regulated, in part, by the levels of mRNA encoding the 5α-reductase enzyme. © 1990 by The Endocrine Society.