Thyroid hormone conversion
T4-to-T3 deiodination
Also searched as T4-to-T3 deiodination.
This is where a thyroid problem often actually lives. The gland can be producing T4 perfectly well while the conversion to the active hormone is running slow.
In depth
The selenium-dependent enzymes that convert T4 into active T3 — and a third that switches it back off.
What drives it
Micronutrient status increases it.
Deiodinase previously had NO upstream edge at all, leaving the thyroid arm unrooted. Verified at source (Redox Biol 2022, doi 10.1016/j.freeradbiomed.2022.09.024 / S0891584922006062): the iodothyronine deiodinases DIO1, DIO2 and DIO3 are a family of selenoproteins — selenocysteine is structural, encoded by in-frame TGA codons, so selenium is not a modulator but a requirement of the enzyme. DIO1 and DIO2 activate T4 to T3; DIO3 inactivates both. Selenium deficiency decreased DIO1 activity in rat liver and kidney, and selenium depletion reduced basal DIO2 expression and activity in a human cell line, reversible by selenium supplementation in a dose- and time-dependent manner. The caveat the review states itself, and it matters for any selenium claim: selenium status has a modest impact on DIO expression and translation. The most thoroughly investigated regulator of DIO1 is T3 itself — the Dio1 gene shows roughly 175-fold induction across the hypo- to hyperthyroid transition. Thyroid hormone status, growth factors and cytokines are named as the main regulators; selenium is a permissive requirement, not the lever. Iodine status has no direct effect on DIO expression, and whether iron status directly affects DIOs remains controversial. doi 10.1016/j.freeradbiomed.2022.09.024
What it drives
It increases Thyroid.
The thyroid does not make most of your active hormone — your tissues do. T4 is a PROHORMONE and must be activated to T3 by type-1 or type-2 selenodeiodinase, and about 80% of circulating T3 is generated outside the thyroid by those two enzymes (PMC3673746; American Thyroid Association-commissioned review, PMC10517335). A third deiodinase inactivates T3 and T4 by removing an inner-ring iodine, so the same enzyme family both switches the hormone on and switches it off. PMC3673746
It increases Body temperature control.
Thyroid hormone is a key regulator of basal metabolic rate and facilitates adaptive thermogenesis; cold and heat intolerance are hallmark clinical features of hypothyroidism and hyperthyroidism respectively. Mullur 2014, Physiol Rev 94:355 — Thyroid hormone regulation of metabolism. doi 10.1152/physrev.00030.2013
It increases Mitochondrial energy.
T3 influences mitochondrial activity and biogenesis by modulating, in a coordinate fashion, expression of proteins encoded by both the nuclear and mitochondrial genome. Lanni 2015, Front Physiol 6:237 — Regulation of skeletal muscle mitochondrial activity by thyroid hormones. doi 10.3389/fphys.2015.00237
It increases Lowers cholesterol.
T3 and T2 promote variations in substrate metabolism and lipid handling at the mitochondrial level in skeletal muscle. Lanni 2015, Front Physiol 6:237 — Regulation of skeletal muscle mitochondrial activity by thyroid hormones. doi 10.3389/fphys.2015.00237
It increases New mitochondria.
T3 controls expression of PGC-1alpha, a central regulator of mitochondrial gene expression; D2-induced local T3 production contributes to PGC-1alpha activation and mitochondrial expansion. Lanni 2015, Front Physiol 6:237 — Regulation of skeletal muscle mitochondrial activity by thyroid hormones. doi 10.3389/fphys.2015.00237
It increases Muscle.
T3 promotes variations in skeletal-muscle substrate metabolism, lipid handling and thermogenesis at the mitochondrial level; thyroid state governs muscle oxidative capacity. Lanni 2015, Front Physiol 6:237 — Regulation of skeletal muscle mitochondrial activity by thyroid hormones. doi 10.3389/fphys.2015.00237
It increases Builds mitochondria.
T3-mediated expression of PGC-1alpha proceeds via a far upstream located thyroid hormone response element. Weitzel 2008, Mol Cell Endocrinol — T3-mediated expression of PGC-1alpha via a far upstream thyroid hormone response element. doi 10.1016/j.mce.2008.01.017
It increases Tissue remodeling.
Mice lacking type 2 iodothyronine deiodinase had a roughly 50% reduction in bone formation rate - the rate at which osteoblasts lay down type-I collagen matrix - caused by local intracellular T3 deficiency despite normal serum T3, showing that deiodinase-generated T3 is required to sustain type-I collagen matrix production. doi 10.1073/pnas.0911346107 · PMID 20368437
It reduces Vessel wall muscle.
Triiodothyronine, the active hormone deiodinase enzymes generate from thyroxine, acted directly on cultured vascular smooth muscle cells and produced cellular relaxation within 10 minutes at 10^-10 M, with no endothelial nitric oxide involvement, showing that thyroid hormone activation relaxes rather than contracts smooth muscle. doi 10.1089/thy.1996.6.505 · PMID 8936680
It increases Growth & survival signaling.
Thyroid hormones acting non-genomically activate PI3K, Akt, mTOR and p70S6K; deiodinase D2 sets the local T3 concentration that drives this. 10.1152/japplphysiol.00643.2007. doi 10.1152/japplphysiol.00643.2007
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.