Somatomedin Generation in Response to Activated and Nonactivated Isohormones of Human Growth Hormone*

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Abstract
The plasmin-cleaved hGH isohormones D and E exhibit several-fold enhanced biological activity in the rat over the major form, isohormone B, but the mechanism of enhanced activity is unknown. The ability of plasmin-cleaved activated hGH isohormones D and E to generate somatomedin activity was compared to that of hGH-B. Hypophysectomized male rats were injected with hGH-E or hGH-B (dose range, 0-100 μg/day), and somatomedin activity in serum was measured by thymidine incorporation into cultured chick embryo fibroblasts. After optimization of the hGH injection schedule, a 7-day injection schedule with one daily dose was adopted. The potency ratio of hGH-E to hGH-B was 3.9 (95% confidence limits, 1.5-28) for somatomedin generation. The two isohormones had been shown to have a potency ratio of 3.2 (95% confidence limits, 2.7-3.9) in the tibial line assay. Neither hGH-E nor hGH-B showed direct somatomedin activity in vitro. It is concluded that activated isohormones exhibit enhanced potency to generate somatomedin in rats, and their growthpromoting and somatomedin-generating activities are comparable. This suggests that a mechanism proximal to somatomedin generation is responsible for expression of the higher biological activity of hGH-E. In addition, an improved method for measuring somatomedin generation in vivo is presented. (J Clin Endocrinol Metab48: 246, 1979)