GROWTH-HORMONE DEPENDENCE OF NON-SUPPRESSIBLE INSULIN-LIKE ACTIVITY (NSILA) AND OF NSILA-CARRIER PROTEIN IN RATS

Abstract

ABSTRACT The effects of hypophysectomy and subsequent growth hormone (GH) treatment on the serum levels of NSILA and of its binding protein were studied in rats. After hypophysectomy NSILA levels fall to 6 % of the normal. Under GH treatment they rise slowly to 65 % of normal after 12 d. In parallel with the changes of serum NSILA, [35S] sulphate incorporation into costal cartilage in vitro is markedly decreased in hypox animals and restored towards the normal by GH treatment. The relative binding activity of [125I] NSILA-S of serum "stripped" from endogenous NSILA is also reduced after hypophysectomy to approx. 30 % of normal, i. e. to a lesser extent than serum NSILA levels. This concentration of binding protein is sufficient to bind trace amounts of labelled NSILA-S. The half-life of an intravenously injected tracer of [125I]NSILA-S is not significantly decreased in hypox animals. Substitution with GH results in a rise of the relative binding activity to normal after 12 d. Chromatography of serum, equilibrated with [125I]NSILA-S tracer, on Sephadex G-200 at neutral pH reveals different radiochromatographic patterns for serum from hypox and normal rats: In hypox rats the main peak of radioactivity appears at 60 % bed volume, in normal rats between 45 and 50 %. During GH treatment this main peak shifts from 60 back to 45–50 %. The distribution of binding activity is similar for normal and hypox rat serum after chromatography on Sephadex G-200 at acidic pH. Furthermore, the binding characteristics of "stripped" hypox and normal serum are identical. This suggests that the same binding protein is present in the normal and hypox rat serum in different molecular forms. It is concluded that GH is a major factor regulating the level of NSILA and of its binding protein in the rat.