THE PITUITARY-MUSCLE AXIS IN MDX DYSTROPHIC MICE

As myogenesis, muscle growth and differentiation and growth factor expression are influenced by thyroid and growth hormone (GH) levels, it is important to investigate the possibility that altered activity of the pituitary-muscle axis prevents the lethal progression of mdr dystrophy and/or contributes to the muscle fiber hypertrophy of limb muscles. The ultrastructure of pituitary and thyroid tissues in age-matched control and mdr mice at 2 and 12 months of age was examined. Pituitary GH, and serum thyroid stimulating hormone (TSH), thyroid hormone (T4), and creatine kinase (CK) levels were measured. Mdx thyroid gland structure was similar to age-matched control glands. Mdx thyroid gland weighed significantly more than in age-matched controls, but was unchanged relative to body weight. TSH and T4 levels were not different from levels in control mice. High CK levels reflected the active dystrophy in mdx muscles. Somatotrophs in mdx pituitaries were hypertrophied in comparison to controls, indicating increased secretory activity, and pituitary GH was slightly but significantly greater in old mdx- female mice compared to age-matched female controls. These observations rule out hypopituitary or hypothyroid function as a reason for the low impact of dystrophin deficiency in mdr muscles. Results suggest a contribution by raised GH to the fiber hypertrophy in mdx limb and heart muscle, which might also assist the large capacity for limb muscle regeneration in mdx mice.