Table 4.

Metabolic properties of natural and synthetic thyroid compounds

	Mechanism of Action	General Actions	Metabolic Actions	Reference Nos.
Naturally occurring
Thyroxine (T4)	Requires conversion by D1 or D2 to T3 for activity at nuclear receptor	May activate PI3K and ERK1/2 pathways	Cell proliferation and angiogenesis	28, 40, 155, 156
	Binds integrin αvβ3 membrane receptor
Triiodothyronine (T3)	Active form of thyroid hormone that binds nuclear TR	Ligand activating thyroid hormone actions in brain, bone, liver, muscle, and heart	Weight loss	28, 38, 40
			Cholesterol and triglyceride reduction
Triac	Binds to the nuclear TR	TSH suppression	Reduction in LDL cholesterol	225
		Does not require MCT8 transporter	Increased bone turnover
			Increase SHBG from liver
DITPA	Binds to the nuclear TR	Does not require MCT8 transporter	LDL cholesterol lowering	96
		Enhances cardiac function	Body weight loss
T1AM	Binds to G protein-coupled trace amino acid associated receptor 1 (TAAR1)	Hypothermia	Transition from carbohydrate to lipid fuel source	25, 88, 217
		Bradycardia	Hyperglycemia
Synthetic
GC1	Binds to the nuclear TR, TRβ selective	Preference for TRβ	Reduce serum LDL cholesterol	260, 270
		Preferential liver distribution and action	Reduce serum triglycerides
		Reduced activity bone and heart
Eprotirome (KB-2115)	Binds to the nuclear TR, TRβ	Preference for TRβ	Reduce serum LDL cholesterol	260, 270
		Preferential liver distribution and action	Reduce serum triglycerides
		Reduced activity bone and heart
MB07811	Binds to the nuclear TR	Preference for TRβ	Reduces LDL cholesterol	32, 270
	Activated in the liver by cytochrome P-450 3A4	Preferential liver distribution and action	Reduces hepatic steatosis

BAT, brown adipose tissue; D1, 5′-deiodinase type 1; D2, 5′-deiodinase type 2; HDAC3, histone deacetylase 3; SHBG, sex hormone binding globulin; T₃, triiodothyronine; T₄, thyroxine; TR, thyroid hormone receptor; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone; UCP1, uncoupling protein 1.