We were having a discussion of this matter just recently and I thought I had achieved an understanding. Then I came across this. Rod, Diogenes, any comments would be appreciated. PR
The thyroid gland secretes a variety of iodinated and non-iodinated molecules that collectively play important roles during prenatal and adult lives. Understanding what these molecules are and what they do informs our understanding of the therapy for hypothyroidism. The main non-iodinated molecule secreted by the thyroid is calcitonin, an endogenous hormone with probable effects on calcium and bone metabolism. The other iodine-containing molecules include T4, T3, reverse T3, 3,3’-diiodothyronine (3,3’-T2), 3,5-diiodothyronine (3,5-T2), monoiodothyronine (T1), and their decarboxylated forms known as thyronamines.
While the traditional view has been that T3 is important as the main iodothyronine with significant binding to nuclear TRs at physiological concentrations, and T4 is important as a precursor of T3 (458), the use of desiccated thyroid extracts for therapy of hypothyroidism is based on the hypothesis that other molecules present in the thyroid gland may have important effects. A growing number of in vitro studies have indicated that administration of pharmacologic doses of 3,5-T2 has metabolic effects, possibly mediated via non-genomic mechanisms, (459-461). Note that the mechanism by which 3,5-T2 is generated in humans is unclear; furthermore the circulating levels of 3,5-T2 is two orders of magnitude lower than T3 (462, 463). Finally, thyronamines have been shown to interact with the G-protein coupled receptor Transcript Antisense to Ribosomal RNA (TAR1), with 3-iodothyronamine being the most potent agonist. In pharmacologic doses 3-iodothyronamine triggers diverse effects such as hypothermia, behavioral inactivity, bradycardia, and decreased cardiac output. Metabolic effects such as a shift from carbohydrate to fat metabolism and stimulation of food intake have also been described (464).
In summary, current evidence supports the classical view that T3 and T4 are the only biologically important secreted products of the thyroid; none of the alternate signaling molecules have been definitely shown to have physiologic relevance in humans at endogenous concentrations. It is not known whether oral use of thyroid extracts would provide any of these “alternate” components to patients, since studies of their retention during product preparation, their absorption into the blood from the gastrointestinal tract, and subsequent concentrations achieved have not been published. The available literature does suggest that pharmacologic administration of 3,5-T2 and iodothyronamines could have metabolic effects.