Enterohepatic circulation of triiodothyronine

The major factor regulating thyroid function is thyroid stimulating hormone (TSH), a glycoprotein released by the thyrotropic cells of the pituitary gland. Determinants of the TSH secretion rate are inhibition by thyroxine (T 4), 3, 3', 5-triiodothyronine (T3), dopamine, glucocorticoids and somatostatin, and stimulation by TSH-releasing hormone (TRH), (nor)adrenaline and perhaps neurotensin [156]. In the control of thyroid hormone bioavailability, an important role is also played by iodothyronine transport into cells, enzymatic deiodination and conjugation. Several groups have studied the enterohepatic metabolic pathways of iodothyronines. It has been generally accepted that these pathways have no more than a passive function in the elimination of the hormone. However, if enterohepatic circulation (EHC) of iodothyronines occurs, the intestinal tract may constitute an important pool of exchangeable hormone. Until recently, only few and inconclusive data existed concerning this EHC. In our studies we have attempted to document the possible existence of an EHC of thyroid hormone and the role it may play in regulating overall hormone metabolism and excretion in the rat. Especially, we wanted to assess the importance of the intestinal microflora for this process. We have studied the biliary clearance of T3 and its conjugates, the hydrolysis of iodothyronine conjugates by intestinal bacteria and intestinal contents, and the metabolism of T3 and its conjugates in conventional (CV) and intestine-decontaminated (ID) rats. It is the purpose of this thesis to discuss the role of the EHC of iodothyronines in thyroid hormone metabolism, with special emphasis on the results of my own studies of this subject, described in detail in the appendix papers.