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 hypob
aric hypoxic environment (HHE) are associated with an altered TPO mRNA expr
ession. 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 leve
ls in the skeletal muscle and small intestine. TPO mRNA and protein were ex
pressed in Purkinje cells and neuronal cells in the brain, in proximal tubu
lar cells and the mesangial cells of the glomeruli in the kidney, in hepato
cytes 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 al
l 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 leve
ls were detected in these three organs. In conclusion, we have demonstrated
that TPO production occurs in Various types of cells. In HHE, however, fac
tors other than TPO may be involved in hypobaric hypoxia-induced thrombocyt
openia in rats.