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E. Martin Spencer, K. O. Uthne and W. C. Arnold


In children with chronic renal insufficiency serum levels of somatomedin measured by radioreceptor assay were found to be strikingly elevated and were in the same range as in acromegaly in spite of decreased growth. The serum somatomedin level was inversely correlated with renal function and children on haemodialysis had the highest values. The elevated somatomedin was most likely due to progressive destruction of the kidney, the primary catabolic site for somatomedin and other polypeptides. After successful transplantation the somatomedin values fell to slightly above normal even though growth was still impaired. Using a bioassay based on the mitogenic property of somatomedin, a lower than normal rather than an increased level was found in chronic renal insufficiency suggesting that in uraemia an inhibitor to somatomedin bioactivity was present. It is concluded that the cause of the growth failure in chronic renal insufficiency and after transplantation is not due to a lack of somatomedin, but an inhibitor to its action could be a factor. It would appear that a normal somatomedin may be necessary for normal growth, but it is not sufficient.

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E. Martin Spencer, Erwin C. C. Si, Chung C. Liu and Guy A. Howard


Insulin-like growth factor-I and parathyroid hormone are both known regulators of bone formation. In this study, human recombinant IGF-I and bovine PTH (1–34) and their combination were studied for their effects in vitro on the proliferation of embryonic chick osteoblast-like cells (osteoblasts) and in vivo on bone formation in normal rats. Osteoblasts from 17-day-old chick embryos were cultured in serum-free BGJb medium containing 0.1% bovine albumin. After 2 days, IGF-I and/or PTH were added. Twenty-four hours later [3H]thymidine incorporation into trichloroacetic acid precipitable material was quantified as an index of cell proliferation. This has previously been shown to reflect actual cell division. IGF-I at doses ranging from 0.85 to 13.6 nmol/l caused a dose-dependent increase in [3H]thymidine incorporation into osteoblasts. PTH alone (10 to 1000 pmol/l) had no significant effect. However, when combined with IGF-I, PTH potentiated the mitogenic effect of IGF-I and achieved statistical significance at 30 and 100 pmol/l (p <0.05). This potentiation was also studied in vivo. The right hindlimbs of rats weighing 150 g were infused intra-arterially by an osmotic minipump with graded doses of IGF-I (0.1 to 0.4 nmol/day) and/or PTH (0.27 nmol/day) for 7 days. The rate of trabecular bone apposition (formation) was measured by double tetracycline labelling and compared with the contralateral uninfused limb which acted as the control. Histomorphometric data revaled that neither IGF-I nor PTH alone had a significant effect on trabecular bone apposition rate compared with control limbs. The co-infusion of IGF-I (0.4 nmol/day) and PTH (0.27 nmol/day) resulted in a marked increase in trabecular bone apposition rate. The results of 2 studies were significant at p < 0.01. These data suggest that PTH potentiates the effect of IGF-I on bone formation both in vivo and in vitro.