Hormonal control of myosin heavy chain genes during development of skeletal muscles.

A pattern of myosin heavy chain (MHC) switching is a hallmark of developing muscles. Factors responsible for these changes in gene expression include endogenous signals, motoneurons and hormones, especially thyroid hormones. After perturbing the innervation and/or thyroid hormone levels we have examined the neonatal-IIb MHC transition during rat development. First, denervation does not qualitatively affect the transition at either the transcriptional or translational level. Second, hypothyroidism prevents the appearance of IIb MHC and its mRNA in the innervated limb; in the denervated hypothyroid limb IIb MHC is synthesized at moderately high levels. Third, hyperthyroidism causes a precocious increase in IIb MHC in both innervated and denervated muscles. These results suggest that the transition from neonatal to adult IIb myosin synthesis is endogenously programmed during development, but is closely orchestrated by the changing neuronal and hormonal status of the animal. Thyroid hormone may exert its influence by effects both on the muscle fibre and on the developing motoneuron. In the guinea-pig the temporalis muscle is sexually dimorphic: it contains a fast-red MHC in the female but a fast-white MHC in the male. This dimorphism has been shown to be mediated by testosterone, since the castrated male synthesizes the fast-red MHC while the testosterone-supplemented female contains the fast-white MHC. During development male and female muscles initially synthesize the fast-red isoform. The male switches to the fast-white form at puberty.