THE METABOLISM OF HUMAN SEX HORMONE-BINDING GLOBULIN IN THE RHESUS-MONKEY

The metabolism of human sex hormone-binding globulin (hSHBG) was studied in eight female rhesus monkeys (Macaca mulatta) after the pulse injection of [I-125]-hSHBG. hSHBG was iodinated with I-125 using a chloramine T technique, and the [I-125]-hSHBG was separated from other constituents by molecular sieve chromatography with a Sephadex G-25 column. The [I-125]-hSHBG was administered intravenously as a pulse in 2 ml of phosphate buffer, pH 7.4, to each of eight rhesus monkeys. Blood samples (2.0 ml) were obtained at 2, 4, 6, 8, 24, 30, 45, and 54 hr after the injection. The glycoproteins were precipitated with concanavalin A-Sepharose, and the radioactivity was measured. The concentration of radioactivity as fraction of dose/ml of serum was plotted on a semilog scale against time. The disappearance of radioactivity could be expressed best as the sum of two exponentials, with a mean +/- SE t1/2 of 2.5 +/- 0.4 and 33.1 +/- 3.7 hr, respectively. The initial volume of distribution was 461 +/- 78 ml and the metabolic clearance rate was 559 +/- 66 ml/day. The very low clearance rate and prolonged t1/2 are compatible with a relative stability in the circulating mass of SHBG. Rapid changes in concentration of SHBG could be due to changes in serum volume, reversible changes in tissue distribution of SHBG, or the secretion of variable forms of desialylated SHBG.