ANDROGEN REGULATION OF NEUROMUSCULAR FUNCTION

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Androgen secretion during development controls the expression of masculine sexual behaviors in most vertebrates. Muscles and nerves are targets for androgen action because they contain specific receptor proteins. Clinical disorders associated with abnormalities in androgen secretion or receptor expression include pseudohermaphroditism, testicular feminization, neuroendocrine and psychosexual abnormalities and alterations in gender identity. An understanding of the basic mechanisms for androgen action can be obtained from studies in animal models and is essential for understanding the basis of human endocrine disorders. The goal of this research program is a molecular understanding of how androgenic steroids control sexually differentiation. In particular, this proposal focuses on hormone- directed differentiation of motor neuron and muscle fiber number in a highly androgen-sensitive experimental system, laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. The numbers of vocal motor neurons and target muscle fibers are sexually dimorphic in adults; sex differences are due to the secretion of androgen from the male testes during development. Expression of an intracellular protein, the androgen receptor, in both muscle and motor neurons permits the direct action of androgens. The goal of the proposed studies is to unravel the interactions between these components - androgen secretion and expression of its receptor, developing muscle and its innervation - responsible for sexual differentiation of the vocal system by examining the control of androgen sensitivity, the role of androgen secretion and innervation in the control of laryngeal muscle fiber number and the role of androgen secretion and muscle fiber addition in the control of laryngeal motor neuron number.