Estrogen is considered to be the primary metabolite responsible for the differentiation of sexually dimorphic brain regions. In contrast, the development of sexually dimorphic nuclei in the spinal cord has been considered to be regulated strictly by androgens. Testing the validity and limitations of this apparent dichotomy in the critical forms of steroid hormones involved in sexual differentiation of the nervous system and potential differences in their site of action is the focus of this proposal. Using a simple hormone-sensitive neuromuscular system in the rat spinal cord, three different features of this system will be examined: aspects of motoneuron morphology (histochemistry), distribution of critical enzymes (immunocytochemistry), and neuromuscular function (electrophysiology). Synergistic effects of estrogen and androgen, the necessity of estrogen availability, the role of supraspinal and local interneuronal, estrogen-sensitive afferents, and the effects of naturally occurring estrogen levels in morphological development will be assessed. Because the transient expression of aromatase has been reported in a variety of developing neural structures, postnatal spinal cords will be assayed for the presence of aromatase. The role of estrogen in regulating the development of gap junctions, which are common in these motoneurons, will also be examined. Changes in motoneuron excitability during development are likely responsible for the onset of spinally mediated reflexes, and the role of estrogen and androgen in the development of several functional properties of these hormone-sensitive motoneurons will be assessed. Because recent evidence suggests that estrogen is in fact involved in spinal cord masculinization, these studies may help in unifying our understanding of the process of sexual differentiation across the developing mammalian central nervous system.
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