Regulation of fetal muscle development by thyroxine

We have demonstrated that fetal hypophysectomy (hypox) induces deficiencies in skin and adipose tissue development and that chronic thyroxine (T4) treatment either normalizes or enhances skin and adipose tissue development in hypox fetuses. Since hypox also induces deficiencies in muscle development we report herein results of a histochemical and biochemical analysis of muscle development conducted in studies of T4-treated hypox fetuses. Pig fetuses were hypophysectomized on day 70 of gestation and treated with T4 during two periods, i.e. 70-90 days and 90-105 days gestational age, by implanting slow-release T4 (15 mg) pellets in the lateral musculature of the hind limb. Blood, muscle and other tissue samples were obtained upon removal of fetuses at days 90 and 105 of gestation. Weights of hypox, control and T4-treated hypox fetuses were similar at the end of the early period (70-90 days) whereas T4 significantly depressed body weight (p < 0.05) during the later period (90-105 days). Muscle weights, protein, DNA and RNA concentrations and muscle fiber size were not influenced by hypox or T4 treatment. Hypox-induced deficiencies in muscle capillary-to-fiber ratios, percentage of dry matter and general morphology were normalized by T4 (p < 0.05) during both treatment periods. Lipid deposition (staining) and histochemical reactivity for an oxidative marker (NADH-TR) were enhanced (p < 0.05) by T4 during both treatment periods as revealed by computer-assisted image analysis. Histochemistry for myofibrillar (acid) ATPase showed that the hypox-impaired type II to type I fiber type conversion was not influenced by T4 treatment. Muscle developmental traits enhanced or normalized by T4 were directly or indirectly related to lipid and/or oxidative metabolism. Effects of T4 on muscle and other tissues indicate, therefore, that thyroid hormones may be key regulators of oxidative and/or lipid metabolism in the neonatal animal.