ANDROGEN REGULATION OF NEUROMUSCULAR FUNCTION

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The goal of our research program is to understand the cellular and molecular events that control sexual differentiation of nerves and muscles. In Xenopus laevis, masculinization of the vocal organ is controlled by gonadal steroids acting through intracellular receptor proteins. We are investigating how secretion of androgenic hormones produces increases in muscle fiber number in developing larynx. Our aims are to discover when androgens act, what cell types are responsible and how the very high androgen receptor protein levels in larynx are regulated. We will measure serum hormone levels during very early development using radioimmunoassay. Androgen action will be blocked at different developmental stages and effects on muscle fiber number assayed. The distribution of androgen receptor containing laryngeal cells will be studied in tissue culture to follow androgen receptor expression at the single cell level. Effects of androgen on myoblast survival, proliferation and fusion will be assayed in vitro. Regulation of androgen receptor expression at the single cell level. Effects of androgen on myoblast survival, proliferation and fusion will be assayed in vitro. Regulation of androgen receptor expression at the messenger RNA level will be examined using Northern analyses and in situ hybridization. Androgen secretion during development controls expression of the masculine phenotype 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 muscular 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 in understanding the basis of human clinical disorders.