How does thyroid hormone influence red blood cell maturation?


View:3830 Time:2017-09-06


Scientists take a big step forward in understanding the connection of thyroid hormone with red blood cell maturation.

The thyroid, a gland located in the neck, produces hormones that regulate metabolic rate and protein synthesis. Thyroid hormones act almost every cell in the body. For example, thyroid hormones regulate production of red blood cells. Patients with thyroid disorders often develop anemia. However, the precise mechanisms underlying this phenomenon remain largely unknown.

To address this question, scientists from Whitehead Institute for Biomedical Research (WIBR), Massachusetts Institute of Technology (MIT) and University of California collaborated together to study red blood cells in culture and in animal models.

Findings of the study appear in the Proceedings of the National Academy of Sciences. The corresponding author is a molecular and cell biologist named Harvey Lodisha, who is a member of WIBR and who is a professor at MIT.

The production of red blood cells (or called erythropoiesis) is a complex process that is tightly regulated by the body. During the differentiation from bone marrow stem cells to mature red blood cells, genes encoding proteins essential for mature red blood cells are switched on. One such protein is hemoglobin, the substance necessary for oxygen transport. Earlier studies have shown that culturing blood cell progenitors in serum in the laboratory switches on the expression of these essential proteins and facilitates the formation of red blood cells.

In this work, scientists sought to determine factors in serum that are vital for red blood cell formation. They used charcoal to filter hydrophobic components from the serum and found that the filtered serum became unable to facilitate red blood cell formation. This suggested that specific hydrophobic components absorbed by charcoal might help red blood cell formation. Furthermore, the addition of thyroid hormone to the filtered serum rescued the production of red blood cells.

Scientists also confirmed that TRβ is a nuclear thyroid hormone receptor. Using a chronic anemia mouse model, they demonstrated that treatment with drugs that activate TRβ stimulated immature blood cell differentiation and reduced anemic symptoms. RNA-seq of human reticulocytes and genome-wide analysis revealed that NCOA4 is a regulator of red blood cell production stimulated by thyroid hormone. Scientists concluded that "TRβ functions together with NCOA4 to regulate red cell formation."

Taken together, the data shows how thyroid hormone stimulates red blood cell production and points to new drug targets for anemia associated with thyroid dysfunction.
 
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