Effects of human serum on transport of testosterone and estradiol into rat brain

Abstract

The effect in vivo of the plasma proteins in human serum on the transport of [3H]testosterone (T), [3H]dihydrotestosterone (DHT) and [3H]estradiol (E2) through the brain capillary wall, i.e., the blood-brain barrier, was studied in anesthetized rats using a tissue-sampling-single-injection technique. In the absence of plasma proteins, .apprx. 90% of plasma T, DHT or E2 was transported into brain on a single pass after a bolus carotid injection of labeled hormone. Serum was obtained from 57 patients in 7 different clinical conditions: pregnancy, oral contraceptive use, thin and obese post-menopausal, follicular phase female, hirsutism and normal male; the level (mean .+-. SD) of sex hormone-binding globulin (SHBG) varied from 17 .+-. 5 nM (hirsutism) to 323 .+-. 83 nM (pregnancy). When the carotid injection solution was made 67% serum, the amount of T, DHT or E2 transported into the brain was inhibited in proportion to the concentration of SHBG. Among the patient groups, an overall linear inverse correlation between the mean SHBG level and the mean extraction of unidirectional influx of T (r [correlation coefficient] = 0.99) and E2 (r = 0.98) was observed. The unidirectional clearance by brain of both T and E2 apparently is inversely related to the SHBG level and the fraction of hormone transported into brain greatly exceeds the free (dialyzable) moiety and is essentially equal to the albumin-bound fraction of plasma T or E2.