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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2289-2296
Human megakaryocytes and platelets contain the estrogen receptor
 and androgen receptor (AR): testosterone regulates AR expression
Gopal Khetawat,
Nauder Faraday,
Michele L. Nealen,
K. Vinod Vijayan,
Everlie Bolton,
Stephen J. Noga, and
Paul F. Bray
From the Departments of Medicine, Pathology, Anesthesiology, and
Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
Gender differences in vascular thromboses are well known, and there
is evidence that platelets may be involved in these differences and
that sex hormones affect platelet function. We characterized the
expression of the estrogen receptor  (ER ), estrogen
receptor  (ER ), progesterone receptor (PR), and androgen
receptor (AR) in the megakaryocyte lineage. Megakaryocytes generated ex
vivo from normal human CD34+ stem cells contained RNA for
ER and AR, which increased with cell differentiation.
Platelets and human erythroleukemia (HEL) cells also
contained ER and AR transcripts. No ER or PR messenger RNA or
protein was detected in the megakaryocyte lineage. Immunofluorescence microscopy showed that ER protein was present in glycoprotein (GP)
IIb+ megakaryocytes and the HEL megakaryocytic cell line
in a predominantly cytoplasmic location. AR showed a cytoplasmic and
nuclear distribution in GPIIb+ and
GPIIb cells derived from CD34+ cells and
in HEL cells. Western immunoblotting confirmed the presence of ER and AR in platelets. Megakaryocyte and HEL AR expression was
up-regulated by 1, 5, and 10 nmol/L
testosterone, but down-regulated by 100 nmol/L testosterone. These
findings indicate a regulated ability of megakaryocytes to respond to
testosterone and suggest a potential mechanism through which sex
hormones may mediate gender differences in platelet function and
thrombotic diseases.
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