Metabolic Fate of Orally Administered Estradiol in Swine3

Abstract

These studies were undertaken to determine the fate of varying amounts of 14C-estradiol-17β (14C-E2) after oral administration to swine. Tranquillized female pigs (5 to 6 weeks old) were given either .04, .4, 4 or 40 μmoles of 14C-E2 via stomach tube, and blood samples were collected from previously implanted jugular cannulae at several time intervals during the first four hours after administration. The gilts were necropsied 4 hours post-treatment and the entire gastrointestinal tract was removed. Free and conjugated estrogens were isolated from the plasma and intestinal chyme. Conjugated estrogens were cleaved by three successive treatments: enzyme, solvolysis and acid hydrolysis. The free estrogens were then identified by their chromatographic mobilities in thin-layer, column- and gas-liquid chromatographic systems, and by recrystallization to constant specific activity. Conclusions based on these studies are that plasma concentrations of radioactive estrogens were very high within 7 min after oral administration of 14C-E2. Estradiol was completely conjugated during absorption and its first pass through the liver. The major steroid conjugates present in plasma regardless of dose were monoglucuronides (>88%), monosulfates (<8%) and diconjugates (<2%). The principal monoglucuronides in plasma were estrone glucuronide (82%), estradiol glucuronide (16%) and estriol glucuronide (3%). The principal monosulfates in plasma were estrone sulfate (52%), estradiol sulfate (34%) and estriol sulfate (16%). The proportion of E2 converted to estrone and the proportion of estrogens conjugated decreased with increasing dose, indicating saturation of responsible enzyme systems of decreased solubility.