Selective changes in binding and immunological properties of human corticosteroid binding globulin by free fatty acids.

Abstract

The steroid hormones, progesterone (P4) and cortisol (F), have different biological activities but are both bound to human corticosteroid binding globulin (CBG) with similar affinity. This study examines the effect of physiological concentrations of FFA on the binding of these steroids to purified CBG and to the serum of pregnant women. It also analyzes the influence of the FFA environment on the immunological behavior of CBG. Unsaturated fatty acids (UFA) had a dose-dependent inhibitory effect (P less than 0.001) on steroid binding to CBG which was offset by saturated fatty acid-induced potentiation of binding (P less than 0.01) when both were present with CBG. UFAs inhibited P4 binding more than F binding. Comparable results were obtained with pregnant serum or with pure CBG. UFAs seemed able, depending on their concentration, to promote different molecular states of CBG, some with enhanced F binding and significantly reduced P4 binding, and others in which both P4 and F binding was markedly reduced. Scatchard analysis of steroid binding to purified CBG indicated that the UFAs influenced the association constant (Ka) and the number of binding sites (n) for F and P4 binding differently. Low concentrations (less than 16 microM) of arachidonic acid (C20:4) slightly potentiated F binding, with no change in Ka and a 1.6-fold increase in n; this concentration of C20:4 reduced n for P4 binding by 40% and did not affect Ka. Higher C20:4 concentrations (greater than 32 microM), reduced the Ka for F binding but did not apparently change n; for P4 binding, Ka was sharply reduced and n increased. The apparent equilibrium dissociation constant (Kd) for both F and P4 binding varied nonlinearly and differently with increasing C20:4 concentration. Immunoelectrophoresis and immunoautoradiography showed a reduction, or loss, of CBG immunoreactivity in the presence of UFA. The extent of these changes varied with the concentration and class of the UFA. These results indicate that FFA induce conformational changes in CBG which may modulate its activity and so influence the role of this protein in both the endocrine and immune systems.