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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE011536-01
Application #
2132883
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1995-09-30
Project End
1998-07-31
Budget Start
1995-09-30
Budget End
1996-07-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Emory University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Widmer, C G; English, A W; Morris-Wiman, J (2007) Developmental and functional considerations of masseter muscle partitioning. Arch Oral Biol 52:305-8
English, Arthur W; Widmer, Charles G (2003) Sex differences in rabbit masseter motoneuron firing behavior. J Neurobiol 55:331-40
Widmer, C G; Carrasco, D I; English, A W (2003) Differential activation of neuromuscular compartments in the rabbit masseter muscle during different oral behaviors. Exp Brain Res 150:297-307
English, Arthur W; Widmer, Charles G (2003) Sex differences in rabbit masseter muscle function. Cells Tissues Organs 174:87-96
Widmer, C G; English, A W; Carrasco, D I et al. (2002) Modeling rabbit temporomandibular joint torques during a power stroke. Angle Orthod 72:331-7
English, Arthur W; Schwartz, Gail (2002) Development of sex differences in the rabbit masseter muscle is not restricted to a critical period. J Appl Physiol 92:1214-22
Pol-Rodriguez, M M; Schwartz, G A; English, A W (2001) Post-translational phosphorylation of the slow/beta myosin heavy chain isoform in adult rabbit masseter muscle. J Muscle Res Cell Motil 22:513-9
Reader, M; Schwartz, G; English, A W (2001) Brief exposure to testosterone is sufficient to induce sex differences in the rabbit masseter muscle. Cells Tissues Organs 169:210-7
Eason, J M; Schwartz, G A; Pavlath, G K et al. (2000) Sexually dimorphic expression of myosin heavy chains in the adult mouse masseter. J Appl Physiol 89:251-8
Eason, J M; Schwartz, G; Shirley, K A et al. (2000) Investigation of sexual dimorphism in the rabbit masseter muscle showing different effects of androgen deprivation in adult and young adult animals. Arch Oral Biol 45:683-90

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