Stimulation of cartilage amino acid uptake by growth hormone-dependent factors in serum: Mediation by adenosine 3′:5′-monophosphate

The effects of growth hormone-dependent serum factors on amino acid transport and on cartilage cyclic AMP levels in embryonic chicken cartilage were studied in vitro. Cartilages incubated in medium containing rat serum showed a significantly greater uptake of α-amino 1-¹⁴C] isobutyrate or 1-¹⁴C] cycloeeucine than control cartilages incubated in medium alone. Normal rat serum (5%) added to the incubation medium also caused an increase in cartilage cyclic AMP content (from as little as 23% to as much as 109%). The factors in serum which increase cartilage cyclic AMP and amino acid uptake are growth hormone dependent, since neither growth hormone itself nor serum from hypophysectomized rats affects either parameter. Growth hormone treatment of hypophysectomized rats restores these serum factors. Studies comparing the ability of sera with varying amounts of growth hormone-dependent factors to stimulate α-aminoisobutyrate transport and to increase cartilage cyclic AMP show a striking linear correlation between the two effects (r = 0.977). Theophylline and prostaglandin E₁, which raise cartilage cyclic AMP also increase α-aminoisobutyrate transport. Exogenous cyclic AMP, N⁶-monobutyrll cyclic AMP and N⁶, O²′-dibutyryl cyclic AMP increase cartilage α-aminoisobutyrate transport. The data are compatible with the thesis that growth hormone-dependent serum factors increase cartilage amino acid transport by elevating cartilage cyclic AMP.