We have investigated the hypothesis that there is local regulation of insulin-like growth factor (IGF) gene expression during skeletal muscle growth. Compensatory hypertrophy was induced in the soleus, a predominantly slow-twitch muscle, and plantaris, a fast-twitch muscle, in 11- to 12-wk-old female Wistar rats by unilateral cutting of the distal gastrocnemius tendon. Animals were killed 2, 4, or 8 days later, and muscles of the nonoperated leg served as controls. Muscle weight increased throughout the experimental period, reaching 127% (soleus) or 122% (plantaris) of control values by day 8. In both growing muscles, IGF-I mRNA, quantitated by a solution-hybridization nuclease-protection assay, rose by nearly threefold on day 2 and remained elevated throughout the experimental period. IGF-II mRNA levels also increased over controls. A more dramatic response was seen in hypophysectomized rats, where IGF-I mRNA levels rose by 8- to 13-fold, IGF-II values by 3- to 7-fold, and muscle mass increased on day 8 to 149% (soleus) or 133% (plantaris) of the control contralateral limb. These results indicate that signals propagated during muscle hypertrophy enhance the expression of both IGF genes, that modulation of IGF-I mRNA levels can occur in the absence of growth hormone, and that locally produced IGF-I and IGF-II may play a role in skeletal muscle growth.
Abstract. To address the question of insulin-like growth factor (IGF) I localization and synthesis in kidney, we used two complementary experimental approaches: immunohistochemistry of fixed paraffinembedded rat kidney sections; and measurement of IGF I mRNA in isolated components of the rat nephron, using a highly sensitive and specific solution hybridization assay. Immunostainable IGF I was localized exclusively to principal cells of cortical and medullary collecting ducts. Administration of growth hormone to hypophysectomized rats for 8 d resulted in enhanced immunohistochemical staining of IGF I within collecting ducts, but no detectable IGF I in other portions of the nephron. The abundance of IGF I mRNA was 7-12-fold higher in isolated papillary collecting ducts than in proximal tubules or glomeruli, and was enriched 10-fold compared with whole kidney. Our data demonstrate colocalization of IGF I and IGF I mRNA in the collecting duct, consistent with focal expression of the IGF I gene at this site.
Chronic stretch of the chicken fast-twitch patagialis muscle increases the rate of growth and percentage of fast-twitch oxidative fibers. We have analyzed the effects of stretch on the expression of two previously identified "embryonic" myosin heavy chain (MHC) mRNAs (p251 and p110). Both MHC mRNAs were expressed in the patagialis at their highest levels in the embryo and 1 wk after hatching. During posthatch development (7-52 wk), the p110 mRNA was expressed in only trace quantities while the p251 mRNA was not detectable. After 2 wk of stretch of the patagialis in 7- or 38-wk-old birds, the p110 mRNA was increased to levels similar to that found in patagialis of newly hatched chicks, whereas expression of the p251 transcript was not affected. The existence of two other MHC mRNAs homologous to the p110 mRNA was suggested by the S1 mapping analysis, one of which was expressed at dramatically reduced levels in the stretched patagialis. It is concluded that stretch can cause selective alterations in the expression of developmentally regulated MHC isoforms in chicken fast-twitch muscle.
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