Developmental expression of genes involved in neurosteroidogenesis: 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase in the rat brain.

In the central nervous system, neurosteroids, in particular progesterone, have neurotrophic and neuroprotective effects. We thus decided to study the developmental expression of 3beta-hydroxysteroid-dehydrogenase/Delta(5)-Delta(4) isomerase (3betaHSD), an enzyme that converts pregnenolone to progesterone, in the male rat brain at 0, 7, 14, and 70 d after birth. 3betaHSD mRNA was widely distributed throughout the brain, as shown by in situ hybridization. At all ages, the same cerebral structures were labeled, but the intensity of the hybridization signal constantly decreased during postnatal development. As the hippocampus is of particular interest because of its neuronal plasticity, we chose to quantify the changes in 3betaHSD mRNA levels as well as progesterone and pregnenolone concentrations in this structure. Quantitative in situ hybridization confirmed a decrease in the expression of 3betaHSD mRNA with progressing age, as revealed by a significant reduction in the density of silver grains per cell in the CA1 layer. This decrease was confirmed by semiquantitative RT-PCR on hippocampal samples. Concentrations of hippocampal pregnenolone and progesterone measured by gas chromatography/mass spectrometry were highest on the day of birth and lower at the other ages. Plasma concentrations of these steroids were lower than those in the hippocampus, suggesting that they may have been mostly synthesized in situ since the day of birth. These results demonstrate variations in the expression of a gene coding for an enzyme critically involved in progesterone synthesis in the hippocampus throughout postnatal development.