Effectiveness of thyroid hormones transporters and deiodinases in skeletal muscle of aging mice

Abstract Background and aim Skeletal muscle (SM) has been shown as a target of thyroid hormones (THs). However, the status and effectiveness of thyroid hormones transporters (THTs) and deiodinases in thyroid hormones signaling system (TH signaling) during aging are uncertain. This study aimed to explore the regulated relationships of TH signaling elements in SM of aging mice.Methods Twenty-four C57BL/6J male mice were divided into 6-, 15- and 24-month (6, 15 and 24M) groups according to different ages. The types and expression of THTs and deiodinases were analyzed by mRNA sequencing and proteomic sequencing. qRT-PCR, Western blotting and fluorescence immunoassay were used to compare the key factors of TH signaling in three groups. The ability of transported THs in THTs was analyzed by [125I] T3 and [125I] T4 uptake rate. The regulatory relationship of TH signaling was analyzed in C2C12 cells.Results We identified eight types of THTs in SM of mice, among which the expression of MCT8, MCT10, LAT2, LAT4 and OATP2B1 increased with age. MCT8, MCT10, LAT2 and OATP2B1 had the ability to take up [125I] T3, while MCT8, MCT10 and OATP2B1 possessed the ability to take up [125I] T4 in C2C12 cells. Expression levels of deiodinase type 2 (DIO2) and type 3 (DIO3) also augmented with aging, and the upregulation of DIO3 was regulated by MCT8 and MCT10. Neither deiodinases nor age-related THTs was regulated by TRα.Conclusions The expression of main types of THTs (MCT8, MCT10, LAT2, LAT4 and OATP2B1) and deiodinases (DIO2, DIO3) significantly increased in SM of aged mice, perhaps due to the compensation of age-related decrease of TRα. The expression of DIO3 was regulated by MCT8 and MCT10.