EFFECT OF GROWTH-HORMONE AND PEPTIDE FRACTIONS CONTAINING SOMATOMEDIN ACTIVITY ON GROWTH AND CARTILAGE METABOLISM OF SNELL DWARF-MICE

In order to obtain more information about a possible role of somatomedin (SM) in vivo, increase in length and weight, costal cartilage activity (35SO4=and 3H-methyl-thymidine incorporation), organ weight and serum glucose levels were studied in Snell dwarfmice, during treatment with human growth hormone (hGH), L-thyroxine (T4), insulin and a semipurified SM-preparation (SM-P1). SM-P1, hGH and T4 caused a significant increase in length and weight, whereas insulin was not effective in a dosage similar to the insulinlike-activity of the SM-P1 preparation measured by radio-receptor assay. The effect obtained with the SM-preparation cannot be due to contamination of GH, prolactin, T4, insulin or testosterone. Costal cartilage activity was measured three days after initiation of treatment by incubation immediately after sacrifice in plasma free medium. Both sulphate and thymidine incorporation were increased by the administration of SM-P1 and hGH, compared to buffer treated controls. After treatment for four weeks no differences between treated and untreated animals in cartilage activity could be observed anymore. Both SM-P1 and hGH induced weight gain in most organs. An outspoken effect was seen on lymphoid organs, the submandibular salivary glands and muscle, a sizeable effect was present on the kidneys and a small effect, not reaching significance for the SM-P1 treated group on brain weight. An impression of divergence was seen with liver weight, which increased on hGH while there was a small and not significant rise on SM-P1. A definite discrepancy was found in skinfold thickness, which was essentially unchanged on hGH and increased on SM-P1. Testes and epididymal fat, though probably increasing their weights, were in insufficient number to do statistics on. Serum T4 is low in untreated dwarfmice. It is increased to a subnormal level after hGH administration whereas no effect is observed with SM-P1. The dose dependent effect of insulin, measured by radioimmunoassay, on the induction of hypoglycaemia is markedly similar to the effect of non-radioimmunoactive insulin-like activity of SM-P1 as measured by radio-receptor assay. The hypoglycaemia induced with insulin and the SM-preparation is reduced by adding 105 glucose to the diet. In conclusion: SM-P1 shows growth stimulating and insulin-like actions in vivo. The pattern of effects obtained with hGH, T4 and insulin differs from that of SM-P1.