Nutrition and Somatomedin. VII. Regulation of Somatomedin Activity by the Perfused Rat Liver*

Abstract

Skeletal growth is currently attributed to stimulation of cartilage proliferation by somatomedins. To assess the potential regulation of circulating somatomedin activity by the liver, rats were subjected to different metabolic conditions, their livers were perfused in situ for 2 h, and samples were obtained every 30 min. Perfusate activity was estimated as the stimulation or inhibition of sulfate uptake by rat costal cartilage in vitro. Perfusates from normal rats provided significant stimulatory (somatomedin) activity after 30 min of perfusion with enriched medium; peak activity after 60 min was 87 ± 20% above that obtained with buffer, and activity declined thereafter. However, perfusates from untreated hypophysectomized rats provided no stimulation, while GH pretreatment resulted in intermediate levels of activity, again with a decline in the second h. Despite the apparent influence of GH in vivo, GH and insulin added in vitro did not increase perfusate activity from either normal or hypophysectomized rats. With both normal and hypophysectomized animals, perfusate activity was higher with enriched medium than with simple buffer. Unlike perfusates from normal rats, perfusates from fasted and diabetic rats provided no stimulation; after 60 min, perfusates decreased cartilage sulfate uptake below buffer levels, and activity became more inhibitory in the second hour. Perfusates from fasted and diabetic rats decreased cartilage stimulation by 45 ± 9% and 61 ± 5%, respectively, when added to incubations containing normal serum, suggesting that these perfusates contained somatomedin inhibitor (s). These studies indicate that liver perfusate net activity reflects metabolic status in vivo more than nutritional/hormonal factors added in vitro over 2 h. The stimulatory (somatomedin) activity in perfusates from normal rats and inhibitory (somatomedin inhibitor) activity in perfusates from fasted and diabetic rats parallel circulating somatomedin activity in these conditions; our observations support the hypothesis that growth regulation via somatomedins is governed at; least in part by the liver, and that hepatic modulation involves the release of both somatomedins and somatomedin inhibitor(s). (Endocrinology106: 260, 1980)