STILBOESTROL TRANSPORT AND GLUCURONIDE FORMATION IN EVERTED SACS OF RAT INTESTINE

¹ Department of Pharmacology, Oakdale Toxicology Center, University of Iowa, Iowa City, Iowa; Department of Biochemistry, St. Mary's Hospital Medical School, London, England

As part of an investigation into the mechanism of the enterohepatic circulation of stilboestrol the passage of stilboestrol and its monoglucuronide conjugate into sacs of everted rat intestine was studied. The sacs were incubated at 37°C for 90 minutes in a solution containing either C¹⁴- stilboestrol or C¹⁴-stilboestrol monoglucuronide. It was found that C¹⁴-stilboestrol readily entered the everted sacs, producing a high concentration of radioactivity in the serosal fluid. By contrast the intestinal sacs were relatively impermeable to C¹⁴-stilboestrol monoglucuronide. The nature of the radioactivity in the serosal and mucosal solutions and in tissue after incubation of everted intestinal sacs with C¹⁴-stilboestrol was determined by chromatography and also, in the case of serosal solutions, by reverse isotope dilution analysis. The relative proportions of stilboestrol and its glucuronide in mucosal solutions depended upon the section of intestine from which the sac was prepared. Tissue contained approximately equal amounts of stilboestrol and glucuronide conjugates, whereas 90% or more of the radioactivity in serosal solutions was present as stilboestrol monoglucuronide. The everted intestinal sac preparation is therefore capable of conjugating stilboestrol with glucuronic acid. These results are discussed in relation to the enterohepatic circulation of stilboestrol in the rat.