The thyroid hormone metabolite Triac stimulates bone mineralisation in larval zebrafish

Triac (3,3',5-triiodothyroacetic acid) is a thyroid hormone metabolite with thyromimetic properties. We investigated the effect of Triac on skeletal formation in larval zebrafish. Compared to other iodothyronines (T4, T3, and 3,5-T2), Triac at nanomolar concentrations stimulated larval zebrafish osteoblast activity in vivo, measured in an sp7:luciferase transgenic line and by the expression of osteoblast-specific genes. The mineralisation of bone elements and whole-body calcium content were enhanced, and the expression of osteoblast and bone matrix marker genes was stimulated. Triac increased the density of integumental ionocytes in the skin epithelium, and the expression of genes involved in calcium uptake increased significantly. No direct effect of Triac on osteoblasts of isolated zebrafish scales was found. The expression of stc1l, encoding the hypocalcaemic hormone stanniocalcin, was suppressed. We propose that Triac affects bone mineralisation by regulating both the uptake of calcium from the ambient water and the exchange of calcium between its major body compartments: bone, blood, and soft tissue. We discuss possible direct and indirect pathways via which Triac affects bone mineralisation. Triac is present in effluents from sewage treatment plants and has biological effects in sub-nanomolar concentrations. We postulate that Triac is an environmental endocrine disruptor.