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 d evelopment of the central nervous system (CNS) is still unclear. One w ay to address this question is to examine the regional and development al expression of enzymes involved in the biosynthesis of these compoun ds. As 5 alpha-reduction is a key step in the formation of dihydrotest osterone and some neurosteroids, we investigated the distribution of 5 alpha-reductase (type 1) messenger RNA (mRNA) in the brains of fetuse s and offspring of timed pregnant Long-Evan rats by means of in situ h ybridization. Our results indicate that during ontogeny, 5 alpha-reduc tase mRNA is expressed in three distinct patterns. 1) During late embr yonic and fetal development, on gestational days 12-18, specific 5 alp ha-reductase mRNA was detected in germinal and ventricular zones of th e 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 specifi c mRNA newly appeared in differentiating regions of the brain, such as the cortical plate and the thalamus. 3) On postnatal day 15 and in ad ult animals, low levels of 5 alpha-reductase mRNA were detected in typ ical white matter structures, such as optical chiasm, lateral olfactor y tract, and corpus callosum. Expression of 5 alpha-reductase mRNA in germinal zones and differentiating fields of the pre- and early postna tal rat CNS has not been described; this suggests that 5 alpha-reducta se might serve a function in general aspects of brain development, e.g . proliferation and differentiation. As several types of steroid hormo nes can serve as substrates for 5 alpha-reductase, it remains to be el ucidated which metabolite(s) mediates the possible actions of the enzy me in CNS development.