Thyroxine Reverses Deficits of Nerve Growth Factor and Epidermal Growth Factor in Submandibular Glands of Mice with Muscular Dystrophy*

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Abstract
Production of nerve growth factor (NGF) and epidermal growth factor (EGF) by granular tubule cells (GTC) in mouse submandibular glands is regulated by hormones. Mice afflicted with hereditary muscular dystrophy have reduced levels of salivary gland NGF and EGF, deficits which are associated with structural alterations in GTC. In this study, we questioned whether growth factor concentrations and GTC abnormalities in dystrophic mice can be altered by hormone treatment. RIA results indicate that T4 treatment of dystrophic mice, both male and female, elevates growth factor levels in submandibular glands to concentrations comparable to those in untreated normal littermates. Testosterone was ineffective in males, but stimulated significant production of NGF and EGF in females, although levels were 4- to 5-fold lower than in testosterone-treated nondystrophic females. Glands in dystrophic females treated with both T4 and testosterone contained NGF and EGF in amounts which were similar to those in normal females receiving only the steroid. Microscopic studies revealed hypertrophy of GTC in both testosterone- and T4-treated dystrophic mice. Cells exhibited expanded endoplasmic reticulum and Golgi elements, and increased numbers of cytoplasmic secretory granules. Results with T4 prompted us to examine blood levels of thyroid hormones in dystrophic mice. Concentrations of total serum T3 were significantly reduced in afflicted males. Dystrophic females, which exhibit greater salivary gland deficits, had lowered blood levels of T3 as well as T4 compared to normal females. Deficits in salivary gland growth factors may arise from previously undescribed thyroid hypofunction in dystrophic mice.