ALPHA-MINERALOCORTICOID, BETA-MINERALOCORTICOID, AND GAMMA-MINERALOCORTICOID RECEPTOR MESSENGER-RIBONUCLEIC-ACID SPLICE VARIANTS - DIFFERENTIAL EXPRESSION AND RAPID REGULATION IN THE DEVELOPING HIPPOCAMPUS

Two different types of corticoid receptor molecules bind circulating c orticosterone in brain: mineralocorticoid receptors (MR) and glucocort icoid receptors. MR exhibit the highest affinity for the endogenous gl ucocorticoid in the rat, corticosterone. During development, low corti costerone levels influence neurogenesis, and these effects are probabl y MR mediated. Three MR complementary DNA clones, alpha, beta, and gam ma, have been identified in the rodent. All of these MR complementary DNA clones have identical coding regions, but differ significantly at the 5'-untranslated end. Although the functional significance of these three messenger RNA (mRNA) species remains unknown, one hypothesis is that they reflect the ability of the brain to regulate the expression of MR, allowing multiple factors to differentially control transcript ion in a tissue- and time-specific manner. To investigate this possibi lity, we examined the presence of these distinct mRNA forms in the dev eloping rat hippocampus (HC). In situ hybridization with specific alph a, beta, and gamma complementary RNA probes was performed in the HC of 3-, 5-, 7-, 12-, 14-, 28-, 35-, and 65-day-old animals. We found that there is differential expression of these forms in each of the HC sub fields from infancy to adulthood. gamma expression appears to be assoc iated with periods of cell birth and increased axonal sprouting. beta expression, on the other hand, may be best linked to periods of synapt ogenesis, growth of commissural and associative terminal fields, and p ossibly active pruning. To explore the possibility that the differenti al gene expression may be related to corticosterone environment, adren alectomy was performed. A rapid modulation of the MR mRNA variants (14 h) in an age- and site-specific fashion was seen. These findings sugg est that the variation in expression and regulation during development of the multiple MR transcripts could reflect a complex pattern of dev elopmental regulation that may involve a multitude of factors unique t o each postnatal age and to the different neuronal populations within the hippocampal formation.