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 u nloaded shortening velocity (V-o) was determined in the rat diaphragm muscle (Dial at 0, 7, 14, 21, and 28 days of age. Hyp was induced by t reating pregnant rats with 6-n-propyl-2-thiouracil (0.05% in drinking water) beginning at gestational day 10 and was confirmed by reduced pl asma levels of 3,5,3'-triiodothyronine and thyroxine. MHC isoforms wer e separated on sodium dodecyl sulfate-polyacrylamide gel electrophores is gels and analyzed by densitometry. Isometric P-o and fatigue resist ance of the Dia were measured in vitro at 26 degrees C, and V-o was de termined at 15 degrees C with the slack test. Compared with control mu scles, 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 ag e, 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 d o not fully predict the changes in Dia contractile properties.