THE PITUITARY-MUSCLE AXIS IN MDX DYSTROPHIC MICE

As myogenesis, muscle growth and differentiation and growth factor exp ression are influenced by thyroid and growth hormone (GH) levels, it i s important to investigate the possibility that altered activity of th e pituitary-muscle axis prevents the lethal progression of mdr dystrop hy and/or contributes to the muscle fiber hypertrophy of limb muscles. The ultrastructure of pituitary and thyroid tissues in age-matched co ntrol and mdr mice at 2 and 12 months of age was examined. Pituitary G H, and serum thyroid stimulating hormone (TSH), thyroid hormone (T4), and creatine kinase (CK) levels were measured. Mdx thyroid gland struc ture was similar to age-matched control glands. Mdx thyroid gland weig hed significantly more than in age-matched controls, but was unchanged relative to body weight. TSH and T4 levels were not different from le vels in control mice. High CK levels reflected the active dystrophy in mdx muscles. Somatotrophs in mdx pituitaries were hypertrophied in co mparison to controls, indicating increased secretory activity, and pit uitary GH was slightly but significantly greater in old mdx- female mi ce compared to age-matched female controls. These observations rule ou t hypopituitary or hypothyroid function as a reason for the low impact of dystrophin deficiency in mdr muscles. Results suggest a contributi on by raised GH to the fiber hypertrophy in mdx limb and heart muscle, which might also assist the large capacity for limb muscle regenerati on in mdx mice.