To develop an animal model for the study of myofascial pain dysfunction (MPD) and temporomandibular disorders (TMD's), we will investigate gender-based differences in the regulation of the phenotype of masticatory muscle fibers by androgenic hormones in rabbits. Immunohistochemical methods will be used to evaluate the myosin heavy chain isoform content of masticatory and line muscle fibers. Quantitative histochemical methods will be used to determine the oxidative and glycolytic enzyme content of the same fibers. This combination of contractile and metabolic protein content is termed phenotype. We will first determine the overall phenotype of male and female masticatory muscle fibers and thereby evaluate the basis of any gender differences. We will then use immunohistochemical methods to determine the androgen receptor content of these fibers and evaluate whether gender-based differences in phenotype can be accounted for by similar differences in androgen sensitivity. The dependence of masticatory muscle fiber phenotype on levels of circulating androgens will be investigated by manipulating hormone levels by castrating and testosterone-treating males or by treating females with dihydrotestosterone. Finally we will begin to evaluate the site of action of androgens in regulating phenotype by blocking muscle fiber receptors selectively, using the antiandrogen, Casodex. MPD and TMD's affects women far more frequently than men, but without an effective animal model in which to study this disorder, determination of any biological basis for gender-specific alterations in muscle structure or function that might underlie the development of MPD has been difficult. It is anticipated that the results of this study will provide such an effective animal and also provide a basis for gender- specific mechanisms in the regulation of masticatory muscle structure and function.
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