Ontogeny of 5 alpha-reductase (type 1) messenger ribonucleic acid expression in rat brain: Early presence in germinal zones

The physiological significance of androgens and neurosteroids in the development of the central nervous system (CNS) is still unclear. One way to address this question is to examine the regional and developmental expression of enzymes involved in the biosynthesis of these compounds. As 5 alpha-reduction is a key step in the formation of dihydrotestosterone and some neurosteroids, we investigated the distribution of 5 alpha-reductase (type 1) messenger RNA (mRNA) in the brains of fetuses and offspring of timed pregnant Long-Evan rats by means of in situ hybridization. Our results indicate that during ontogeny, 5 alpha-reductase mRNA is expressed in three distinct patterns. 1) During late embryonic and fetal development, on gestational days 12-18, specific 5 alpha-reductase mRNA was detected in germinal and ventricular zones of the developing CNS. Specific labeling was also detected in the liver and certain ganglia, such as those of the trigeminal and spinal nerves. 2) During late fetal and early postnatal development, 5 alpha-reductase mRNA levels in the ventricular zones gradually decreased, but specific mRNA newly appeared in differentiating regions of the brain, such as the cortical plate and the thalamus. 3) On postnatal day 15 and in adult animals, low levels of 5 alpha-reductase mRNA were detected in typical white matter structures, such as optical chiasm, lateral olfactory tract, and corpus callosum. Expression of 5 alpha-reductase mRNA in germinal zones and differentiating fields of the pre- and early postnatal rat CNS has not been described; this suggests that 5 alpha-reductase might serve a function in general aspects of brain development, e.g. proliferation and differentiation. As several types of steroid hormones can serve as substrates for 5 alpha-reductase, it remains to be elucidated which metabolite(s) mediates the possible actions of the enzyme in CNS development.