EXCEED THE SPACE PROVIDED. Testicular steroids exert effects throughout the body, regulating cell physiology and structure in numerous target organs. For example, androgens have anabolic effects on skeletal muscle, and also affect the nervous system, which among other things, determines sexual phenotype of the brain and regulates behavior. In one such neuromuscular system in rats, the sexually dimorphic SNB system, some androgen effects on neurons are mediated through skeletal muscles. For example, androgens act on the muscle in development to ensure that motoneurons survive and to cause those same motoneurons to extend dendrites in adulthood. Androgens also work directly on muscle in development to ensure its survival and to determine its overall size in adulthood. However, it is not known what cells in muscle have androgen receptors (ARs). Answering this question represents the first step toward understanding how androgens work in muscle to influence the muscle directly and the motoneurons indirectly. Immunocytochemistry (ICC) will be used to identify the cells in rat muscles that express ARs, comparing the levator ani (LA) to the extensor digitorum Iongus (EDL), which differ in their sensitivity to androgens. ICC will also be used to characterize the role of androgens and innervation on AR expression; both influence the androgen sensitivity of skeletal muscles. Reverse transcriptase polymerase chain reaction (RT-PCR) will also be used to quantify AR message. We will test directly the role of ARs in muscle fibers by transfecting in vivo AR genes into AR-deficient mutant muscle fibers. Because muscle wasting occurs in Kennedy's Syndrome (caused by a mutation in the AR gene) and in amyotrophic lateral sclerosis (ALS), these studies aimed at identifying and understanding the mechanisms by which androgens spare motoneurons and muscle fibers from death, and promote their growth in adulthood, may suggest new therapeutic measures for individuals suffering from such pathologies. This path holds particular promise, since the human homologue to the rodent SNB is completely spared in individuals that die of ALS. This finding suggests a potentially important relationship between ARs in muscle and the growth and/or demise of the muscle and its motoneurons. PERFORMANCE SITE ========================================Section End===========================================
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