Thrombopoietin expression in normal and hypobaric hypoxia-induced thrombocytopenic rats.

Thrombopoietin (TPO) is important as the physiologic regulator of platelet production. High-altitude hypoxia is a well-known cause of polycythemia and thrombocytopenia in animals. Fifty-two Wistar rats were housed for 0.5 to 21 days in a mechanical chamber in an environment equivalent to that found at 5500 m to determine (a) the cellular localization of TPO and (b) whether the decreased platelet and megakaryocyte counts in rats exposed to a hypobaric hypoxic environment (HHE) are associated with an altered TPO mRNA expression. In normal rats, there were high levels of TPO mRNA in the liver and kidney, intermediate levels in the brain and large intestine, and low levels in the skeletal muscle and small intestine. TPO mRNA and protein were expressed in Purkinje cells and neuronal cells in the brain, in proximal tubular cells and the mesangial cells of the glomeruli in the kidney, in hepatocytes and biliary duct epithelial cells, in absorptive epithelial cells in the large intestine, in the epidermis, and in the lung. The platelet count in the blood and megakaryocyte counts in the bone marrow and spleen were all decreased significantly after 5 or more days of exposure to HHE. In major producers such as the liver and kidney and in minor producers such as the brain, TPO mRNA levels, which tended to be decreased after 0.5 to 3 days of exposure to HHE, had returned to normal by about Day 5 or 7. Thus, during the HHE period with a decreased platelet count, no changes in TPO mRNA levels were detected in these three organs. In conclusion, we have demonstrated that TPO production occurs in various types of cells. In HHE, however, factors other than TPO may be involved in hypobaric hypoxia-induced thrombocytopenia in rats.