Rat enterohepatic circulation and intestinal distribution of enterally infused thyroid hormones

The enterohepatic circulation (recycling), intestinal (gut) distribution, metabolism, and excretion of enterally infused thyroid hormones were studied in the intact rat under approximately normal physiological steady state conditions. Rats with 7-day osmotic minipumps implanted ip received constant intraduodenal infusions to steady state of very small trace doses of either 125I-labeled T3 (T3*) or T4 (T4*). Enterohepatic and other pathways remained open to normal function, and in particular, there was no biliary diversion or ligation. Complete feces and urine were collected daily, to assess daily distributions of radioactivity and establishment of the steady state, which occurred by day 3. On day 7, rats were anesthetized, blood was sampled, whole intestine and minipumps were removed, and the gut was separated into six segments. Fecal samples and the contents of each gut section were homogenized, ethanol extracted, evaporated, and reconstituted in NaOH for quantitative aqueous chromatography along with infusate, urine, and plasma samples, on Sephadex G-25 columns. No T3* or T4* was found in urine, but feces contained 39% of the T3* infused and 36% of the T4* infused in steady state. Statistically significant amounts of both T3* and T4* in systemic plasma on day 7 clearly indicated absorption of the hormones from the intestine, distinctly demonstrating an enterohepatic circulation of T3 and T4 under experimental conditions closely approximating the physiological steady state. This also establishes the intestine (with its contents) as an exchangeable hormone pool, physiologically internal to the system regulating thyroid hormones and their distribution. Gut contents contained 52 times more T3* and 4.34 times more T4* than corresponding plasma pools in steady state. Kinetic analysis of the data indicated that somewhat more than half of the T3* or T4* infused was absorbed from gut to liver (primary absorption), and up to 34% of the T3* infused and 43% of the T4* infused reached the systemic circulation (secondary absorption/bioavailability). Gut contents longitudinal distribution data 1) confirm existing evidence that thyroid hormone conjugates, formed elsewhere, exist in gut contents and are hydrolyzed there; 2) demonstrate that deconjugation becomes quantitatively significant, and thus may be initiated, at the level of the cecum; and 3) strongly suggest that absorption of unconjugated hormone occurs from at least the small intestine, all under normal physiological conditions.