Stimulation of DNA synthesis in isolated chondrocytes by somatomedin. II. Validation of the assay for clinical use and comparison with stimulation of protein synthesis.

The effects of GH on cartilage may be mediated by a variety of serum factors (somatomedins; SM). We have reported (Endocrinology 90: 1086, 1972) stimulation of thymidine incorporation in isolated chicken embryo chondrocytes by normal human serum. This was greater than that caused by serum from patients with hypopituitarism. We have now compared the stimulatory activity estimated by [3H]thymidine incorporation (SMT) with that estimated by [3H]leucine incorporation in 46 sera from children with GH deficiency; with short stature, but normal GH responsiveness; or with normal stature and normal GH responsiveness. These activities were also measured in sera from 9 normal adults and 12 acromegalics. Sera from GH deficient children had reduced SMT activity (.54 +/- .04; (mean +/- SE) P less than .01) compared to normal children (.83 +/- .08) whereas the sera from children with short stature and normal GH responsiveness had higher levels than normal (1.19 +/- .10: P less than .02). Acromegalic adults averaged higher SMT activity than normal adults (1.62 +/- .15 vs. 1.17 +/- .11; P less than .05). In sharp contrast, the leucine incorporation was essentially the same in the different groups of children. These studies have validated the use of the incorporation of thymidine into isolated chicken embryo chondrocytes as an adjunct in the evaluation of children with short stature (82.6% of the samples from children gave results that were consistent with their status as determined by provocative tests for GH). The disparity between the results with thymidine incorporation and those with leucine incorporation is as yet unexplained.