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 from C57BL/6 mice. Both cell lines are capable of metabolizing testosterone to 6α-hydroxytestosterone, 6β-hydroxytestosterone and androstenedione. The formation was found to correlate with protein concentration and time of incubation. These linearities were significant for all metabolites except androstenedione that was the main metabolite in embryonic hippocampal neurons and nearly absent in postnatal neurons. Moreover, only embryonic cells react to testosterone with a decrease of β- tubulin expression, that was a typical effect indicating induced neuronal maturation. Application of androstenedione caused the same decrease of β- tubulin expression as testosterone did before. Our results of hippocampal testosterone metabolism in vitro confirm that not only estradiol and 5α- dihydrotestosterone could impact neural tissue but also androstenedione is a powerful metabolite involved in prenatal neuronal differentiation. (C) 2000 Wiley-Liss, Inc.