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Alternate pathways of thyroid hormone metabolism
Sing-Yung Wu1, William L Green, Wen-Sheng Huang
1Nuclear Medicine and Medical Services, University of California, Irvine and Department of Veterans' Affairs Healthcare System, Long Beach, California 90822, USA. sing.wu@med.va.gov
Thyroid : Official Journal of the American Thyroid Association
|September 1, 2005
Summary
Thyroid hormone metabolism involves deiodination, sulfation, and glucuronidation, influencing active hormone bioavailability. Sulfation is key in fetal development, while glucuronidation aids excretion and can impact thyroid function, especially in hypothyroid patients.
Area of Science:
- Endocrinology
- Metabolic Biochemistry
Background:
- Thyroid hormones (THs), primarily thyroxine (T4) and triiodothyronine (T3), regulate numerous physiological processes.
- Deiodination of T4 to T3 is the primary mechanism controlling active TH bioavailability in mammals.
- Alternative metabolic pathways, including sulfation, glucuronidation, deamination, decarboxylation, and ether link cleavage, also modulate TH activity and availability.
Purpose of the Study:
- To explore the diverse metabolic pathways of thyroid hormones beyond deiodination.
- To elucidate the regulatory roles of sulfation and glucuronidation in TH metabolism.
- To investigate the physiological significance of less common TH derivatives and metabolic routes.
Main Methods:
- Review of existing literature on thyroid hormone metabolism.
- Analysis of the biochemical transformations of T4 and T3 through sulfation, glucuronidation, and other pathways.
- Examination of the clinical implications of these metabolic routes in fetal development, drug interactions, and disease states.
Main Results:
- Sulfation of T4 and T3 accelerates deiodination to inactive metabolites and is prominent in fetal development, potentially regulating T3 supply and facilitating maternal-fetal exchange.
- Glucuronidation facilitates biliary-fecal excretion of THs; its stimulation can lower TH levels and affect TSH secretion, particularly in rats and hypothyroid humans.
- Conjugates (sulfated and glucuronidated THs) can act as reservoirs for active iodothyronines, and derivatives like triac show therapeutic potential in hormone resistance syndromes.
Conclusions:
- Thyroid hormone metabolism is complex, involving multiple pathways that fine-tune the availability of active hormones.
- Sulfation and glucuronidation play significant roles in regulating TH levels, particularly during fetal development and in response to xenobiotics.
- Understanding these diverse metabolic routes is crucial for comprehending thyroid hormone physiology and developing targeted therapies.