Effect of somatomedin and growth hormone on bone collagen synthesis in vitro

Although pituitary hormones, particularly growth hormone (GH), are known to influence skeletal growth, there is no evidence for a direct effect of GH or GH-dependent factors (somatomedins) on bone as opposed to cartilage. We have examined the effects of GH, a somatomedin (Sm) preparation, and serum from intact and hypophysectomized rats on bone collagen synthesis in cultures of 21-day fetal rat calvaria. Collagen synthesis and non-collagen protein synthesis were measured by the incorporation of ³H-proline into collagenase-digestible (CDP) and noncollagen protein (NCP). Bovine and rat GH caused a small inhibition in the incorporation of labeled proline into CDP which was not dose related. Sm in doses of 18–540 mU/ml increased the incorporation of proline into CDP up to three-fold after 24 hr in culture. Sm also had a smaller and more variable stimulatory effect on the labeling of NCP. The effects of Sm were maximal after 3 hr of treatment and were maintained for 96 hr. Sm (60 mU/ml) and insulin (10^?8 M) had effects of similar magnitude and were not additive. The addition of 10% serum from hypophysectomized rats stimulated the labeling of both CDP and NCP, but serum from rats with intact pituitaries had a greater effect. Treatment of hypophysectomized rats with thyroxine, corticosterone, and GH. did not increase the bone collagen synthesis stimulating activity of the serum, although GH treatment did increase serum Sm activity by a pig cartilage assay. The results indicate that GH dose not stimulate bone collagen synthesis directly. However, they suggest that the pituitary gland either releases or stimulates the production of factors which stimulate bone collagen synthesis. Sm may be such a factor, but sulfation activity and bone collagen synthesis stimulating activity may be dissociable.