Effects of spaceflight and thyroid deficiency on rat hindlimb development.II. Expression of MHC isoforms

Both slow-twitch and fast-twitch muscles are undifferentiated after birth a s to their contractile protein phenotype. Thus we examined the separate and combined effects of spaceflight (SF) and thyroid deficiency (TD) on myosin heavy chain (MHC) gene expression (protein and mRNA) in muscles of neonata l rats (7 and 14 days of age at launch) exposed to SF for 16 days. Spacefli ght markedly reduced expression of the slow, type I MHC gene by similar to 55%, whereas it augmented expression of the fast IIx and IIb MHCs in antigr avity skeletal muscles. In fast muscles, SF caused subtle increases in the fast IIb MHC relative to the other adult MHCs. In contrast, TD prevented th e normal expression of the fast MHC phenotype, particularly the IIb MHC, wh ereas TD maintained expression of the embryonic/ neonatal MHC isoforms; thi s response occurred independently of gravity. Collectively, these results s uggest that normal expression of the type I MHC gene requires signals assoc iated with weight-bearing activity, whereas normal expression of the IIb NM C requires an intact thyroid state acting independently of the weight-beari ng activities typically encountered during neonatal development of laborato ry rodents. Finally, MHC expression in developing muscles is chiefly regula ted by pretranslational processes based on the tight relationship between t he MHC protein and mRNA data.