The activity of the c-Mpl ligand on hematopoietic progenitors meets cr
iteria expected for thrombopoietin (TPO), Bioassays have shown that bl
ood TPO levels are inversely related to platelet mass. We sought to id
entify the molecular basis for this regulation. To determine if TPO mR
NA levels respond to platelet demand, RNA from selected organs of mice
with high, normal, or low platelet counts was subjected to semiquanti
tative reverse transcriptase-polymerase chain reaction, Although no di
fferences in TPO mRNA levels between control and treated mice could be
detected in liver or kidney, TPO-specific bands were more intense aft
er 25 to 30 polymerase chain reaction cycles in marrow-derived mRNA fr
om thrombocytopenic mice. The TPO-specific bands were less intense in
thrombocytotic mouse marrow and spleen than control mouse marrow and s
pleen after 30 cycles. These data support the hypothesis that TPO leve
ls are regulated, at least in part, by modulating mRNA levels in respo
nse to platelet demand. (C) 1995 by The American Society of Hematology
.