Effects of Chronic Infusions of Sex Steroid-Binding Protein on the Testosterone-Mediated Inhibition of Gonadotropin Secretion and Maintenance of Sex Accessory Glands in Male Rats*

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Abstract
Sex steroid-binding protein (SBP) is a plasma glycoprotein which, in man and many other mammals, binds significant amounts of circulating testosterone (T) with high affinity. To evaluate the effects of T binding by SBP on the control of reproductive function in males, SBP was purified from human plasma and administered by chronic infusion to castrated T-treated rats, animals that lack endogenous SBP. Plasma T concentrations in males implanted with 20-mm T capsules and infused with vehicle for 48 h were maintained at 1.37 .+-. 0.14 ng/ml, and plasma LH and FSH concentration remained at intact levels. Castrates implanted with identical T capsules but infused with human (h) SBP at a rate that produced a steady state plasma hSBP concentration of 75 nM, had markedly higher plasma T concentrations (3.44 .+-. 0.32 ng/ml); however, circulating LH and FSH concentrations were not significantly different from those of the vehicle-infused controls. Similarly, the pituitary LH response to a bolus injection of LHRH was not affected by SBP infusions. Measurements of tissue concentrations of T, dihydrotestosterone, and 3.alpha.-androstanediol in the ventral prostate and seminal vesicles, as well as the weights of these organs, failed to reveal any effects of hSBP infusions on the uptake, metabolism, or action of T. Analysis of T distribution in plasma showed that the hSBP infusions produced marked increases in total plasma T levels but resulted in only marginal reduction in the concentration of T not bound to hSBP. These results are consistent with the hypothesis that T not bound to SBP is the major feedback-effective moiety and that under conditions of constant release of T into the circulation, an increase in plasma T binding by SBP increases the total plasma T concentration but does not appear to significantly after the feedback-effective levels of T in the circulation. Therefore, it would appear that moderate changes in the amount of high affinity binding of T in the circulation would have little, if any, effect on androgen balance in adult males.