Excretion, Metabolism and Enterohepatic Circulation Pathways and Their Role in Overall Thyroid Hormone Regulation in the Rat

Regulation of thyroid, adrenocortical and other hormones secreted by the major endocrine glands in mammals is widely attributed primarily to feedback control relationships with the pituitary, hypothalamus or both, with hepatobiliary and intestinal mechanisms having no more than a passive or excretory role. I present another view of enterohepatic components in thyroid endocrine function, suggesting a functional and more pervasive role for the intestine, in a more complex hierarchical system controlling thyroid hormone levels, effects and economy in the rat, and possibly in other mammals. A central factor is the existence of enterohepatic cycling of these hormones, or their reabsorption from intestnal pools to portal and then systemic blood. This process affects their dynamic behavior throughout the organism, not only hormone economy, because bidirectional transport of hormone between blood and intestine (including large pools in luminal contents) renders all or part of the gut internal to the system regulating thyroid hormones. We review the evidence for and possible significance of this hypothesis, covering specific aspects of hormone level control in the rat, including the deiodination, conjugation and other metabolic pathways, particularly in liver and intestine, and the fecal and urinary excretory (sink) and hormone production (source) pathways. The modulators of enterohepatic subsystem regulation of thyroid hormones are postulated to involve the combined effects of hormone conjugation and degradation processes in liver and their subsequent secretion in bile, coupled with the bacterial deconjugation, the reabsorption and certain hormone storage mechanisms of the intestine.