Main Factors Involved in Thyroid Hormone Action

The thyroid hormone receptors are the mediators of a multitude of actions by the thyroid hormones in cells. Most thyroid hormone activities require interaction with nuclear receptors to bind DNA and regulate the expression of target genes. In addition to genomic regulation, thyroid hormones function via activation of specific cytosolic pathways, bypassing interaction with nuclear DNA. In the present work, we reviewed the most recent literature on the characteristics and roles of different factors involved in thyroid hormone function in particular, we discuss the genomic activity of thyroid hormone receptors in the nucleus and the functions of different thyroid hormone receptor isoforms in the cytosol. Furthermore, we describe the integrin αvβ3-mediated thyroid hormone signaling pathway and its rapid nongenomic action in the cell. We furthermore reviewed the thyroid hormone transporters enabling the uptake of thyroid hormones in the cell, and we also include a paragraph on the proteins that mediate thyroid receptors’ shuttling from the nucleus to the cytosol.

Hematopoiesis in aged female mice devoid of thyroid hormone receptors

Hypothyroidism is often associated with anemia and immunological disorders. Similar defects are found in patients and in mice with a mutated dominant-negative thyroid hormone receptor α (TRα) and in knockout mice devoid of this receptor, suggesting that this isoform is responsible for the effects of the thyroid hormones in hematopoiesis. However, the hematological phenotype of mice lacking also TRβ has not yet been examined. We show here that TRα1/TRβ-knockout female mice, lacking all known thyroid hormone receptors with capacity to bind thyroid hormones, do not have overt anemia and in contrast with hypothyroid mice do not present reduced Gata1 or Hif1 gene expression. Similar to that found in hypothyroidism or TRα deficiency during the juvenile period, the B-cell population is reduced in the spleen and bone marrow of ageing TRα1/TRβ-knockout mice, suggesting that TRβ does not play a major role in B-cell development. However, splenic hypotrophy is more marked in hypothyroid mice than in TRα1/TRβ-knockout mice and the splenic population of T-lymphocytes is not significantly impaired in these mice in contrast with the reduction found in hypothyroidism. Our results show that the overall hematopoietic phenotype of the TRα1/TRβ-knockout mice is milder than that found in the absence of hormone. Although other mechanism/s cannot be ruled out, our results suggest that the unoccupied TRs could have a negative effect on hematopoiesis, likely secondary to repression of hematopoietic gene expression.