Different testosterone metabolism by immortalized embryonic and postnatal hippocampal neurons from C57BL/6 mice: A crucial role for androstenedione

Steroid hormones influence the development of undifferentiated brain during ontogenesis. In the present study we investigated the metabolic pathway of testosterone in immortalized embryonic and postnatal hippocampal neurons f rom C57BL/6 mice. Both cell lines are capable of metabolizing testosterone to 6 alpha-hydroxytestosterone, 6 beta-hydroxytestosterone and androstenedi one, The formation was found to correlate with protein concentration and ti me of incubation. These linearities were significant for all metabolites ex cept androstenedione that was the main metabolite in embryonic hippocampal neurons and nearly absent in postnatal neurons. Moreover, only embryonic ce lls react to testosterone with a decrease of beta-tubulin expression, that was a typical effect indicating induced neuronal maturation. Application of androstenedione caused the same decrease of beta-tubulin expression as tes tosterone did before. Our results of hippocampal testosterone metabolism in vitro confirm that not only estradiol and 5 alpha-dihydrotestosterone coul d impact neural tissue but also androstenedione is a powerful metabolite in volved in prenatal neuronal differentiation. J. Neurosci. Res. 60:106-115, 2000. (C) 2000 Wiley-Liss, Inc.