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

The relative abilities of three test substances ([‘4C] antipyrine, I‘4Cl barbital and [3H1 manni-tol) 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 O.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 I ‘4C1 antipyrine and [‘4C1 barbital steady-state conditions for radioactivity concentrations in uterine fluid were nearly achieved by 80 mm after injection. At this time, the ratios of uterine fluid to serum radioactivity concentrations for these relatively lipophilic sub-stances were marginally less than 1.0, indicating that equilibration between serum and uterine fluid radioactivity had nearly occurred. In contrast, these ratios at 80 mm ranged between 0.30 and 0.31 for the least lipophiic substance tested, [3H] mannitol. The ratios of uterine fluid to serum radio-activity concentrations at 5 mm 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 I ‘4C1 antipyrine> I Cl bar-bital> I HI mannitol; this ranking of compounds corresponds exactly with that of their lipid solu-bilities. For 114 CI antipyrine and [14 CI barbital, as indicated by the ratios of uterine fluid to serum radioactivity concentrations at 5 mm after injection, steady-state conditions were approached more rapidly in estradiol plus progesterone-treated animals than in those receiving progesterone only. These results indicate the importance of lipid solubiity as a factor in addition to molecular size which influences the ability of a substance to cross the blood-uterine lumen barrier