Estradiol has been shown to act in the central nervous system to promote neuronal growth, differentiation, and synaptic plasticity. Recent evidence indicates that estrogens exert these effects by enhancing the expression of genes that encode key proteins of the neuronal cytoskeleton and synaptic membranes. In a previous report, we demonstrated a sex-related difference in the developmental expression of Class II β-tubulin (RBT1) mRNA, which encodes a neural-specific tubulin isotype. This difference, not shared by Class IV β-tubulin mRNA or the mRNAs encoding neurofilament proteins, was restricted to the hypothalamus. RBT1 mRNA levels were found to decrease in both sexes during postnatal development, but significantly earlier in females than in males, suggesting that the difference is steroid-dependent. The present experiments demonstrate that 17β-estradiol increases, in a stereospecific manner, RBT1 mRNA levels in the hypothalamus of developing female rats. The effect was also region-specific, as it was not detected in either the cerebral cortex or the cerebellum. The increase in RBT1 mRNA levels was observed after either in vivo administration of 17β-estradiol or in vitro exposure of the hypothalamus to the steroid, and it was evident during both neonatal-infantile development (4 to 12 days of age) and near the time of puberty (29 days of age). The effect was detected by RNA blot hybridization and verified by a sensitive, sequence-specific ribonuclease (RNase) protection assay. In vitro exposure of hypothalamic fragments containing the arcuate/ventromedial nucleus-median eminence region of 28-day-old animals to 17β-estradiol prevented the decline in RBT1 mRNA levels that follows selective blockade of mRNA synthesis via pharmacological inhibition of RNA polymerase II. The results suggest that the neurotrophic effects exerted by 17β-estradiol during early postnatal development of the hypothalamus and in the arcuate/ventromedial nuclei at the time of puberty are, at least in part, mediated by an increase in RBT1 mRNA levels, the consequence of an estradiol-dependent increase in RBT1 mRNA stability.
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology