In vitro influence of plasma steroid-binding proteins on androgen metabolism in human leukocytes

The purpose of this study was to investigate the influence of plasma steroid-binding proteins on androgen metabolism in intact leukocytes prepared from normal male and female blood samples. Leukocyte preparations were incubated for 24 h at 37 degrees C with either labeled or unlabeled testosterone (T), 5 alpha-dihydrotestosterone (5 alpha-DHT), and androstenedione (A). After extraction, the formed labeled metabolites were first identified by high performance liquid chromatography, then, using unlabeled substrates, metabolite concentrations were measured by specific radioimmunoassays. The conversion ratios of substrate to metabolite were calculated for each preparation using either labeled or unlabeled substrates. In the absence of steroid-binding proteins, the mean conversion ratios of T to A, A to T, T to 5 alpha-DHT, and 5 alpha-DHT to 3 alpha-androstanediol (3 alpha-D) were, in males and females, respectively, 5.6% and 6.1% (n = 11), 5.6% and 5.6% (n = 5), 2.8% and 2.2% (n = 11), 43.1% and 40.0% (n = 5), these sex differences being non-significant. The presence of increasing amounts of plasma, purified albumin or sex hormone binding-globulin (SHBG) in the incubation media reduced metabolite formation dose-dependently. However, a 1000-fold greater concentration of albumin than of SHBG was necessary for 50% inhibition of androgen metabolism by leukocytes, showing SHBG to have the main protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)