This proposal examines the characteristics, ontogeny and mechanisms of androgen-induced laryngeal proliferation. Our focus is on muscle and its androgen receptors. Experimental approaches include tritiated thymidine autoradiography androgen receptor assays, electron microscopy, steroid autoradiography and tissue culture. We will induce proliferation in the larynx of juveniles and characterize the temporal parameters of the response. Mitogenesis in different cell types (e.g., myoblasts, fibroblasts) will be examined at the light and electron microscopic level. The ontogeny of androgen-induced proliferation will be studied and related to sexual dimorphism and reproductive physiology at puberty. We will measure androgen receptors in laryngeal muscle and analyze receptor affinity and specificity in males and females at different ontogenetic states and in response to endocrine stimulation. Relations between androgen receptors and proliferation in myoblasts and fibroblasts will be examined in vitro. The long term objective of our research is to uncover mechanisms whereby hormones regulate sexual differentiation of neuroeffectors for reproductive behavior. We believe that a focus on the motor neuron-muscle unit will provide powerful advantages in such analyses. Results of these studies should shed light on steroid modulation of myogenesis and regeneration and on endocrine complications of neuromuscular disease.
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