Extraction of somatomedin activity from rat liver

Biologically active somatomedins were evaluated after extraction from rat tissues. Somatomedin activity was measured by bioassay as stimulation of sulfate uptake by hypophysectomized rat costal cartilage. Somatomedin activity was found in the liver after extraction with acid but not with neutral media. Activity was not found in acid extracts of spleen, muscle, brain, or kidney. While acetic acid liver extracts from normal rats had significant activity, extracts from hypophysectomized rats had no activity; treatment with GH in vivo restored hepatic activity to normal. After gel filtration on Sephadex G-75 in 1 M acetic acid, somatomedin activity recovered from liver extracts was of a somewhat higher molecular weight (approximately 30,000) than activity in serum fractions (approximately 8,000). Extract somatomedins produced dose-response stimulation of cartilage parallel to that by serum somatomedins; the total hepatic content of somatomedin activity was over twice as great as the total serum activity. Cartilage-inhibiting (somatomedin inhibitory) activity was also found in extract fractions; the apparent molecular weight was approximately 50,000. Hypophysectomized rats given liver extract somatomedins in vivo exhibited modest but significant increases in costal cartilage sulfate uptake, an index of growth activity. These observations of a substantial hepatic content of somatomedin activity which is 1) GH dependent, 2) not found in other tissues, and 3) biologically active both in vitro and in vivo support the concept that serum somatomedins originate in the liver.