Hormonal Regulation of Somatomedin Secretion by Fetal Rat Hepatocytes in Primary Culture*

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Abstract
To determine which hormones might regulate somatomedin secretion the fetus, somatomedin levels were measured in conditioned medium from primary cultures of fetal rat hepatocytes. A bioassay ([3H]thymidine incorporation into DNA of chick embryo fibroblasts), a displacement assay [competition for binding of radiolabeled multiplication-stimulating activity (rat insulin-like growth factor II) to the somatomedin-binding protein] for total somatomedin and the RIA [radioimmunoassay] for somatomedin-C were employed. Epidermal growth factor and dexamethasone were the most active hormones tested; total somatomedin levels were 2-3 times above control levels. Rat GH [growth hormone] was much less stimulatory. Human placental lactogen, glucagon and insulin had little or no effect. Stimulation of somatomedin secretion by both epidermal growth factor and dexamethasone was time- and dose-dependent. The maximal response occurred at 48 h at a concentration of about 1 .times. 10-7 M of either hormone. In the bioassay, stimulation by epidermal growth factor, but not dexamethasone, was detected. The steroid enhanced the secretion of an inhibitor that completely masked the mitogenic activity of the increased somatomedin levels. The somatomedin secreted by fetal hepatocytes exhibited immunological cross-reactivity with human somatomedin-C, but the levels were 500-fold less than those measured by a displacement assay. Apparently, the predominant fetal rat somatomedin is not somatomedin-C. Epidermal growth factor and dexamethasone, but not GH or placental lactogen, stimulated the secretion by fetal hepatocytes of a somatomedin which resembled multiplication-stimulating activity.