SEX-DIFFERENCES IN GLUTAMIC-ACID DECARBOXYLASE MESSENGER-RNA IN NEONATAL RAT-BRAIN - IMPLICATIONS FOR SEXUAL-DIFFERENTIATION

Sexual differentiation of rodent brain is dependent upon hormonal expo sure during a ''critical period'' beginning in late gestation and endi ng in early neonatal life. Steroid hormone action at this time results in anatomical and physiological sexual dimorphisms in adult brain, bu t the mechanism mediating these changes is essentially unknown. The in hibitory neurotransmitter, GABA, is involved in regulation of sexually dimorphic patterns of behavior and gonadotropin secretion in the adul t. Recent evidence suggests that during development GABA is excitatory and provides critical neurotrophic and neuromodulatory influences. We hypothesized that steroid-induced changes in GABAergic neurotransmiss ion during this critical period are important mediators of sexual diff erentiation in brain. Therefore, we quantified levels of mRNA for GAD, the rate-limiting enzyme in GABA synthesis. On Postnatal Day 1, males had significantly higher levels of GAD mRNA in the dorsomedial nucleu s, arcuate nucleus, and CA1 region of hippocampus. On Postnatal Day 15 , after the critical period for sexual differentiation has ended, thes e differences were no longer present. We examined the role of gonadal steroids in regulating GAD by removing testes of males and administeri ng testosterone to females at birth. Exposure to testosterone was corr elated with increased GAD mRNA in the dorsomedial nucleus. A sex diffe rence in GAD mRNA was also observed in the medial preoptic area, but t he influence of testosterone was inconclusive. We conclude that sex di fferences in the GABAergic system during development are partially hor monally mediated, and that these differences may contribute to the dev elopment of sexually dimorphic characteristics in adult brain. (C) 199 6 Academic Press.