COEXPRESSION OF MHC ISOFORMS IN NEONATAL MUSCLE SINGLE FIBERS: EFFECTS OF HYPOTHYROIDISM ON DEVELOPMENTAL TRANSITIONS

Abstract

1524 The objective of this study was to examine, at the single fiber level (n=2,203), neonatal-to-adult transitions in myosin heavy chain isoform expression under normal and hypothyroid conditions. Analyses were performed at 5, 10, 20, and 40 days postpartum. The majority (>95%) of fibers co-expressed the embryonic and neonatal MHC isoforms at 5 and 10 days postpartum. The transition to the adult state was complete by 20 days of age. At this time point, the embryonic and neonatal MHC isoforms were completely repressed, and most fibers (76%) co-expressed the IIX and IIB isoforms. Hypothyroidism blunted this developmental transition with many (>95%) fibers continuing to co-express the neonatal and embryonic isoforms. The findings of this study suggest that: 1) a tight transformation process exists between the neonatal and Type IIB MHC isoforms; 2) the down-regulation of the embryonic isoform seems to be coupled to the up-regulation of the adult fast Type IIX and IIA MHC isoforms; 3) the thyroid hormone plays a strong role in controlling developmental up-regulation of the fast IIB MHC isoform along with a weaker role in the developmental up-regulation of the fast Type IIA and IIX MHC isoforms. Supported by NIH NS33483 and NASA NAG2-949