Tissue uptake of human sex hormone-binding globulin and its influence on ligand kinetics in the adult female rat

The distribution of human sex hormone-binding globulin (hSHBG) and its influence upon the kinetics of its ligands were assessed in the adult female rat, which lacks a comparable protein in serum. Purified hSHBG was administered i.v. to adult female rats as a single bolus. The plasma disappearance rate of immunoreactive hSHBG had one component with a half-life of 15 h. The estradiol (E₂) binding activity of serum attributable to hSHBG was elevated 2-fold; during a continuous infusion of E₂, hSHBG increased E₂ serum levels above those of control infused animals. Treatment with hSHBG did not modify the plasma clearance of endogenous E₂, but accelerated the disappearance rate of 5α-dihydrotestosterone (DHT). In animals injected with a tracer dose of radioactive steroids, pretreatment with hSHBG increased uterine and oviductal accumulation of E₂- but not DHT-associated radioactivity. This effect was specific to some E₂ target tissues since hSHBG did not alter the concentration of E₂- or DHT-associated radioactivity in the hypophysis, liver, diaphragm, or brain. Treatment with anti-E₂ antibodies, which elevated E₂ binding activity in serum, decreased the accumulation of E₂-associated radioactivity in uterus and oviduct. Immunofluorescent localization of hSHBG revealed intense labeling of the uterine and oviductal epithelium. We conclude that this foreign hormone- binding globulin introduced in serum at concentrations that have minimal circulating reservoir effect on E₂ can reach intracellular domains and affect the concentration of this ligand in target tissues.