Hypothyroidism alters diaphragm muscle development

The impact of hypothyroidism (Hyp) on myosin heavy chain (MHC) isoform expression, maximum specific force (P(o)), fatigability, and maximum unloaded shortening velocity (V(o)) was determined in the rat diaphragm muscle (Dia) at 0, 7, 14, 21, and 28 days of age. Hyp was induced by treating pregnant rats with 6-n-propyl-2-thiouracil (0.05% in drinking water) beginning at gestational day 10 and was confirmed by reduced plasma levels of 3,5,3'- triiodothyronine and thyroxine. MHC isoforms were separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and analyzed by densitometry. Isometric P(o) and fatigue resistance of the Dia were measured in vitro at 26°C, and V(o) was determined at 15°C with the slack test. Compared with control muscles, expression of MHC-slow was higher and expression of adult fast MHC isoforms was lower in Hyp Dia at all ages. The neonatal isoform of MHC continued to be expressed in the Hyp Dia until day 28. At each age, P(o) and fatigability were reduced and V(o), was slower in the Hyp Dia. We conclude that Hyp-induced alterations in MHC isoform expression do not fully predict the changes in Dia contractile properties.