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Estrogen modulates the recruitment of myelopoietic cell progenitors in rat
through a stromal cell-independent mechanism involving apoptosis
NK Shevde and JW Pike
Department of Biochemistry, Ligand Pharmaceuticals Inc, San Diego, CA
92121, USA.
Loss of ovarian function leads to a significant increase in the number of
bone-resorbing osteoclasts. Estrogen replacement is known to manifest bone
protective effects in the treatment of postmenopausal osteoporosis. In the
present study, we used ovariectomized rats to examine the effects of
estrogen loss at the osteoclast progenitor colony forming unit-granulocyte
macrophage (CFU-GM) level. A significant increase in CFU-GM number was
observed as early as 7 days following ovariectomy, and correlated directly
with an increase in the number of osteoclast-like cells generated in marrow
cultures. The increase in CFU-GM following ovariectomy was abrogated in
animals that received estrogen treatment in vivo. A similar suppressive
effect was observed on CFU-GM number when ovariectomized rat marrow was
treated with estrogen in vitro. This effect was blocked in the presence of
the estrogen antihormone ICI 164,384. Thus, the data suggest the
possibility that estrogen exerts a direct effect on osteoclast progenitors,
and does so through the estrogen receptor-mediated mechanism. Ovariectomy
also led to an increase in the early hematopoietic stem/progenitor cell
population (Thy 1.1+ cells) as determined by FLOW cytometry methods.
Morphological changes as well as terminal deoxynucleotidyl transferase
assays revealed that estrogen treatment negated growth factor-induced
proliferation of these early progenitors by promoting apoptosis. The
cellular effects of estrogen in vitro together with the immunocytochemical
detection of the estrogen receptor in these cells, strongly support the
contention that in addition to osteoclast progenitors such as CFU-GM,
earlier hematopoietic progenitors are also unique cellular targets for
estrogen action.
Volume 87,
Issue 7,
pp. 2683-2692,
04/01/1996
Copyright © 1996 by The American Society of Hematology
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