The effect of membrane permeability and binding by human serum proteins on sex steroid influx into the uterus.

To determine the effect of such factors as capillary membrane permeability, plasma protein binding, and capillary transit time on the availability of sex steroids to the uterus, the unidirectional influxes of 3H-labeled steroids from the circulation into the uterus were measured in vivo in anesthetized rats using a tissue-sampling, single injection technique. When dihydrotestosterone (DHT), estradiol (E2), and progesterone (P) were injected with Ringer's solution, the tissue extraction was in excess of 80%; hence, membrane permeability did not play a limiting role. With the more polar steroids, corticosterone and cortisol, uterine extraction was less than 40%. Significant inhibition of tissue extraction of DHT and E2, but not P, occurred with the addition of 4% albumin to the injection solution. Human sera containing increasing concentrations of sex hormone-binding globulin demonstrated inhibition of extraction of DHT and E2. Human sera also inhibited P extraction, presumably secondary to the presence of cortisol-binding globulin and orosomucoid. Large concentrations of unlabeled DHT, E2, and P in the injection solutions did not result in competitive inhibition of labeled steroid extraction. Thus, there is no evidence for a carrier mechanism mediating steroid transport into the uterus. When tissue extraction of E2 from Ringer's solution was compared in liver, brain, and uterus, no difference of tissue permeability could be found. Liver consistently had higher tissue E2 extraction than brain or uterus in the presence of human sera. The results are compatible with the influx of albumin-bound E2 into all three tissues and the influx of sex hormone-binding globulin-bound E2 into the liver.