Nutrition and somatomedin: nutritionally regulated release of somatomedins and somatomedin inhibitors from perfused livers in rats.
Circulating somatomedin activity reflects the presence of both somatomedins and somatomedin inhibitors, factors which antagonize the growth-promoting actions of somatomedins. Although both are regulated by nutrition, somatomedin inhibitors respond more rapidly than somatomedins to refeeding in fasted animals. To explore the role of the liver in such responses, release of somatomedin activity and somatomedin inhibitor activity was assessed during perfusion of livers from normal, fasted, and fasted-refed rats. Size-exclusion high-performance liquid chromatography (HPLC) revealed that liver perfusates contain both somatomedin and somatomedin inhibitor activity of apparent molecular weight (mol wt) comparable to that found in the circulation (approximately 7,000 and approximately 30,000, respectively), as well as activity of apparently higher wt. In subsequent studies, responses to nutrition were evaluated as fluctuations in bioactivity only of mol wt comparable to that found in the circulation. Release of both somatomedin and somatomedin inhibitor activity was progressive over at least two hours of recirculating perfusion. Perfusates of livers from normal fed rats had somatomedin activity (stimulation of cartilage SO4 uptake) 94 +/- 19% above buffer (P less than .01), which fell to undetectable levels after three days of fasting. With refeeding, perfusate somatomedin activity rose within three hours to approximately 25% of levels in fed rats, but did not become significant until after 12 hours (29 +/- 7%, P less than .02). Perfusates of livers of fed rats also contained somatomedin inhibitor activity (42 +/- 10% inhibition of cartilage stimulation by normal serum), which rose after three days of fasting to 114 +/- 22% (P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)