Direct effect of sex steroid-binding protein (SBP) of plasma on the metabolic clearance rate of testosterone in the rhesus macaque

We report direct evidence for the effect of the sex steroid-binding protein (SBP) on the metabolic clearance rate of testosterone (MCR T). Pure rhesus SBP or human SBP was infused intravenously into three different cycling female rhesus monkeys. MCR T was measured before and after SBP had reached 150–300% of basal levels. A decrease in MCR T was observed in all cases. The effect of SBP on MCR T was tested further in four additional cycling females by infusing immunoaffnity-purified monospecific human SBP antibodies known to cross-react with rhesus SBP. SBP dropped to 54, 40, 4 and 2% of basal levels with a concomitant increase of 118, 190, 320 and 640% of basal MCR T. In one of these animals, pure rabbit SBP was administered after the anti-human SBP infusion resulting in a decrease in MCR T. The magnitude of the SBP effect on MCR T is related to the distribution of testosterone (T) bound to SBP and albumin in the plasma. Calculations show that as long as the percent of T bound to SBP is equal or higher than the percent of T bound to albumin, the influence on MCR T is small. However, if SBP is reduced to the extent that T is bound mostly to albumin, the redistribution of T is associated with a dramatic increase in MCR T. We conclude that under normal conditions each animal has an optimum concentration of plasma SBP which binds a maximum amount of T. If SBP increases above this level, little effect on MCR T will result. However, a drop below the optimum level, as is the case in certain physiological or clinical conditions, will produce a large increase in the clearance of T.