Selective Permeability of the Blood-Uterine Lumen Barrier in Rats: Importance of Lipid Solubility 1

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Abstract
The relative abilities of three test substances ( [14C] antipyrine, [14C] barbital and [3H] mannitol) having similar molecular weights (range of 182-188) but with differing lipid solubilities (partition coefficients between chloroform and phosphate-buffered saline, pH 7.4 of 17.2, 0.23 and approximately equal to 0.002, respectively) to enter the uterine lumen from blood were examined in immature ovariectomized and nephrectomized rats treated for 3 days with progesterone alone or combined with estradiol. With [14C] antipyrine and [14C] barbital steady-state conditions for radioactivity concentrations in uterine fluid were nearly achieved by 80 min after injection. At this time, the ratios of uterine fluid to serum radioactivity concentrations for these relatively lipophilic substances were marginally less than 1.0, indicating that equilibration between serum and uterine fluid radioactivity had nearly occurred. In contrast, these ratios at 80 min ranged between 0.30 and 0.31 for the least lipophilic substance tested, [3H] mannitol. The ratios of uterine fluid to serum radioactivity concentrations at 5 min after injection in animals receiving the same hormone treatment indicated that steady-state conditions were approached at differing rates depending upon the test substance. The test substances ranked according to these ratios were [14C] antipyrine greater than [14C] barbital greater than [3H] mannitol; this ranking of compounds corresponds exactly with that of their lipid solubilities. For [14C] antipyrine and [14C] barbital, as indicated by the ratios of uterine fluid to serum radioactivity concentrations at 5 min after injection, steady-state conditions were approached more rapidly in estradiol plus progesterone-treated animals than in those receiving progesterone only.(ABSTRACT TRUNCATED AT 250 WORDS)

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