Control of serum copper (Cu) and selenium (Se) status by thyroid hormones

Copper and selenium are trace elements essentially needed for the expression and activity of a number of important and rate-limiting human enzymes. Among the Cu-dependent proteins are the bilirubin, lysyl and catechol oxidases, the endocrine relevant enzymes dopamine-beta and peptidyl-glycine mono-oxygenases and the antioxidant enzyme superoxide dismutase. In serum, Cu is mainly transported by hepatically-derived ceruloplasmin (CP). Se is needed for the expression of selenoproteins including the deiodinases implicated in thyroid hormone (TH) activation and inactivation, the glutathione peroxidases needed for the physiologically controlled degradation of peroxides and the thioredoxin reductases controlling the intracellular redox status. Se is transported by selenoprotein P (SePP), a tightly controlled Se-containing serum protein and Se biomarker. In rodents, we have previously observed a stringent regulation of hepatic CP and SePP expression by TH. Now, we tested whether TH also affect serum Se and Cu concentrations in healthy humans.

T4 (250 microg/day) was given to 16 healthy male probands for 8 weeks. Blood was drawn at baseline, after 4 and 8 weeks of treatment, and after 12 and 16 weeks, i.e., during follow-up. The effects of T4 on serum Se and SePP were of borderline significance, while Cu increased significantly upon T4 treatment in all but the one subject with highest baseline Cu values (P = 0.000***). Notably, the inter-individual differences between baseline, follow-up and treatment values of serum Se, Cu and SePP concentrations decreased during the active T4 treatment period. Apparently, T4 treatment harmonized the serum concentrations of these trace elements, verifying an effective interaction of TH with the availability and metabolism of these two essential micronutrients.

We conclude that serum Cu and Se concentrations are affected by the TH status in healthy human individuals, potentially affecting Se and Cu transport from liver to the other organs including the endocrine glands. Expression of peripheral selenoproteins may thereby be affected contributing to the clinical symptoms of hypo- and hyperthyroidism, which normalize under adequate therapy.

Funded by the Deutsche Forschungsgemeinschaft (DFG, Scho849/4 – 1).