Cartilage Sulfation and Serum Somatomedin in Rats During and After Cortisone-Induced Growth Arrest

Abstract

The uptake of sulfate by rib cartilage in vitro and in vivo and the serum somatomedin activity by bioassay were determined in male rats during and after cortisone-induced growth arrest. Experimental treatment consisted of subcutaneous injections of cortisone acetate in a dose of 2.5 mg/rat/day for 4 days, beginning at 29 to 30 days of age in Buffalo rats, or 5 mg/rat/day for 4 or 5 days, beginning at 39 to 41 days of age in Long-Evans rats. Groups of hypophysectomized rats were studied in parallel in one experiment. The sulfate uptake in the controls declined linearly with increasing age in both the in vitro and the in vivo studies. Hypophysectomy resulted in a constant low level of sulfate uptake in vitro. At the end of cortisone treatment, the in vitro sulfate uptake was approximately midway between that of the hypophysectomized rats and that of controls; at 7 days recovery, it was at the control level; at 14 days it showed an additional rise above the control value; from 14 days to 35 days it declined parallel with but above the sulfate uptake of controls. The in vivo sulfate uptake was depressed by cortisone treatment. During recovery it approximated control values at recovery day 21. In succeeding recovery periods in vivo sulfate uptake remained at control levels. Serum somatomedin activity was significantly reduced during cortisone treatment; it returned to the control level by 21 days of recovery. The incubation of the cartilage of controls and cortisone-treated rats at 14 days of recovery with and without the presence of normal rat serum, cortisone recovery serum, or hypophysectomy serum resulted in significantly higher sulfate uptake in the cortisone-treated rat cartilage in each medium. These sera did not differ significantly in their stimulation of sulfate uptake in either cortisone recovery cartilage or control cartilage. Both treated and control cartilage had greater sulfate uptake with larger doses of serum added to the medium. The dose-response curves were parallel during treatment and early recovery; but the slopes of the dose-response curves of the cartilage of cortisone-treated rats were greater than those of the controls during late recovery. It is concluded that the increased in vitro sulfation after 14 days of recovery in cortisone-treated rats signifies a persistent alteration in cartilage metabolism. Normal in vivo sulfate uptake during that time may be the result of humoral controls. A mechanism other than the impairment of somatomedin production is probably involved in the failure of catch-up growth after glucocorticoid treatment in the rat.