Hereditary pituitary dwarfism in mice affects skeletal and cardiac myosin isozyme transitions differently.
The dwarf mutation in mice interferes with the development of those anterior pituitary cells responsible for production of thyroid stimulating hormone, growth hormone, and prolactin. Myosin isozyme transitions in both cardiac and skeletal muscle were also found to be affected in this mutant. Electrophoresis of native myosins demonstrated that the fetal (V3) to adult (V1) ventricular cardiac isozyme transition was completely blocked in dwarf mice; in contrast, the neonatal to adult fast myosin transition in hind limb skeletal muscle was slowed but not totally inhibited. The persistence of neonatal myosin heavy chain for up to 55-75 d after birth in dwarf mice, as compared with 16 d in normal mice, was directly demonstrated by polypeptide and immunopolypeptide mapping. Morphological examination of 18-36-d-old dwarf skeletal muscles by optical and electron microscopy revealed a relative immaturity, but no signs of gross pathology were evident. Immunocytochemical analysis showed that the abnormal persistence of neonatal myosin occurs in most of the fibers. Multiple injections of thyroxine restored a normal isozyme complement to both cardiac and skeletal muscles within 11-15 d. Therefore, the effects of the dwarf mutation on myosin isozymes can be explained by the lack of thyroid hormone in these animals. Because the synthesis of growth hormone is not stimulated by thyroid hormone in dwarf mice as it would be in normal animals, these results demonstrate that thyroid hormone promotes myosin isozyme transitions independent of growth hormone production.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D004195:Disease Models, Animal; D004393:Dwarfism, Pituitary / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D004591:Electrophoresis, Polyacrylamide Gel; D006651:Histocytochemistry; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D024510:Muscle Development; D009132:Muscles / Q000201:enzymology* / Q000648:ultrastructure; D009206:Myocardium / Q000201:enzymology*; D009218:Myosins / Q000032:analysis / Q000378:metabolism*; D013974:Thyroxine / Q000008:administration & dosage
D007527:Isoenzymes; D009218:Myosins; D013974:Thyroxine