To assess the in vivo effect of plasma proteins on the tissue availability of circulating estradiol in postmenopausal women with endometrial cancer, the transport of tritiated estradiol across the brain capillary wall, ie, the blood-brain barrier, was examined in anesthetized rats using a tissue samplingsingle injection technique. Serum samples were studied from 25 women with endometrial cancer and from an equal number of women without the disease who were matched to the cancer patients for age and percent ideal weight. The mean ± SE brain uptake indices of estradiol, using serum from the cancer patients and controls, were 40.7 ± 2.8 and 33.9 ± 2.6, respectively. This difference was not statistically significant. Positive correlations were observed between the brain uptake index and percent ideal weight in the cancer (r=.65) and in the control (r=.21) subjects. Linear regressions of the reciprocal of the brain uptake index and levels of sex hormone-binding globulin showed strong correlations (r=.78) in both groups of patients, whereas correlation coefficients between the brain uptake index and percentage sex hormone-binding globulin werer=.86 andr=.98 for the cancer and the control subjects, respectively. These latter observations support the concept that the brain uptake index reflects the effects of plasma proteins on transport of estradiol across a capillary wall. The findings of this study indicated that 1) the fraction of estradiol available for transport across the blood-brain barrier greatly exceeded the free (dialyzable) moiety and was essentially equal to the albumin-bound and free (dialyzable) fractions of the plasma hormone; and 2) the tissue availability of estradiol was influenced by the body size of the subjects, particularly in the cancer patients, with more circulating estradiol being available in the obese women. This observation suggests that obese, older women are at dual risk of the action of estradiol at the tissue level. They have higher total levels and proportionately greater bioavailable fractions than slender subjects.
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