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Non-saturable transport of [³H]oestradiol across the blood—brain barrier in female rats is reduced by neonatal serum

Summary. Adult ovariectomized rats were decapitated 5 sec after intracarotid injection of a 200-µl bolus containing [³H]oestradiol plus [¹⁴C]butanol, which served as a freely diffusible reference for transport across the blood–brain barrier. When buffered Ringer's solution (with 20% ethanol added to dissolve the oestradiol) was used as the injection vehicle, 83 ± 6% (mean ± s.e.m.) of the injected [³H]oestradiol (0·17 µM) reaching the brain microvasculature was extracted in one circulatory passage. Addition of unlabelled oestradiol (34 or 68 µM) to the injection bolus did not reduce this percentage of extraction. When 0·1% bovine serum albumin rather than ethanol was added to buffered Ringer's solution to ensure solubilization of [³H]oestradiol (0·043 µM), the percentage brain extraction was 82 ± 6%, and again, addition of unlabelled oestradiol (300 µM) did not reduce this value significantly. This finding suggests that oestradiol diffuses into the rat brain passively and is not transported via saturable carrier molecules. When serum from an adult, ovariectomized, female rat was used as the injection medium, the brain extracted 56 ± 4% of the injected [³H]oestradiol (0·17 µM), whereas only 13 ± 1% was extracted from a pool of serum obtained from 9-day-old young rats of both sexes. Brain extraction of [³H]oestradiol (0·043 µM) was significantly lower when the injection vehicle used was serum collected from female rats killed on Days 0, 5 or 20 after birth than on Days 30 or 120. These in-vivo results suggest that neonatal rat serum contains a factor (presumably -fetoprotein) that restricts oestradiol influx into the developing brain.

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