Effects of Peptide Anabolic Hormones on Growth of Myoblasts in Culture

Abstract

The roles of growth hormone and somatomedin in stimulating muscle cell proliferation were investigated in a series of experiments on myoblast growth in culture. At levels 100 times normal circulating concentrations, neither growth hormone nor insulin stimulated growth of rat muscle cells in serum-free medium. In contrast, Temin's Multiplication Stimulating Activity (MSA), a close biological and chemical analog which served as a somatomedin surrogate in this study, was active at concentrations corresponding to the reported circulating levels of the somatomedins; MSA gave consistent stimulation of myoblast proliferation, protein accumulation, and [3H]thymidine incorporation by rat myoblasts and by Yaffe's L6 myogenic cell line. (The unreliability of [3H]thymidine in corporation as a quantitative assay for mitogenic activity is illustrated.) Addition of insulin at physiological concentrations and at the very high levels often used to stimulate cell growth did not enhance the effects of MSA on myoblast proliferation; effects were barely additive. We interpret these results to support earlier indications from studies on diaphragm muscle that the somatomedins are physiologically important mediators of the growth-promoting actions of growth hormone in muscle.

The role of polyamines in somatomedin‐stimulated differentiation of L6 myoblasts

“…We also showed that MSA stimulated both L6 proliferation (Florini et al, 1977;Florini and Ewton, 1981) and differentiation as measured by increased fusion and elevated CK activity. In an attempt to establish more clearly any relationship between these observations, we measured the time course of changes in ODC levels as myotubes formed.…”

Hormonal Control of Immunoreactive Somatomedin Production by Cultured Human Fibroblasts

“…FIGURE 6 Gel filtration chromatography of medium on Sephacryl S-200. Medium that had been exposed to fibroblast cultures for 24 FIGuRE 7 Gel filtration chromatography of medium on Sephadex G-50.…”

“…Since immunoreactive somatomedin production may be a rate-limiting factor for fibroblast growth, the delineation of the hormonal control of somatomedin production should lead to a better understanding of the mechanisms controlling human fibroblast growth. INTRODUCTION The somatomedins, a family of growth hormonedependent, insulinlike peptide growth factors, have been shown to be mitogenic for a variety of types of cultured cells (1)(2)(3)(4)(5)(6). Cartilage from various species and fibroblasts derived from chick (7) and mouse (8) embryos fail to synthesize DNA or undergo mitosis normally when incubated in somatomedin-deficient serum.…”

Recombinant growth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans.

“…Although in vitro data are conflicting with regard to the direct anabolic properties of GH (6-8) and suggest that many of the biological activities of this hormone may be mediated by secondary mediators such as insulin-like growth factors (IGFs) (7)(8)(9), it is clear that administration of this peptide to animals (10) and humans (11) promotes weight gain and whole body nitrogen retention. However, a mechanistic analysis of these effects in humans has previously been limited partly by the restricted quantities of the hormone and by possible contaminants in pituitary extracts of this hormone (12).…”