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Scientists uncover novel role for estrogen in bone marrow

Scientists have discovered a new role for estrogen in maintaining health. Drs. Yuka Nagata and Kazuo Todokoro report in the December 1 issue of Genes & Development that the most abundant form of naturally occurring estrogen, estradiol, triggers the formation of blood platelet cells. This discovery has important clinical implications for the treatment of conditions associated with altered platelet counts, like anemia, certain leukemias, and even chemotherapy.

Blood is composed of 3 cell types: red blood cells, white blood cells, and platelets. Platelets circulate in the bloodstream to facilitate clotting and halt bleeding. Platelets are derived from a specialized bone marrow cell called a megakaryocyte. A mature megakaryocyte extends long cytoplasmic processes (termed proplatelets) from its cell surface that, in one of the most dramatic morphological changes known to cell biologists, simultaneously fragments into thousands of new platelet cells.

Dr. Nagata and colleagues set out to identify the cellular signal of this remarkable event. Previous work identified a gene regulator (what scientists refer to as a transcription factor) named p45 NF-E2 as being expressed in megakaryocyte cells and required for proplatelet formation. However, the target(s) of p45 NF-E2 were, until now, unknown.

Dr. Nagata found that the 3b-HSD gene is normally turned-on by p45 NF-E2 during megakaryocyte development. 3b-HSD encodes an enzyme that regulates all steroid hormone biosynthesis. Thus, Dr. Todokoro and colleagues explored which steroid hormones are produced in megakaryocyte cells. Much to their surprise, they found estrogen.

Dr. Nagata and colleagues determined that 3b-HSD induces the production of estrogen, in the form of estradiol, in both male and female megakaryocyte cells. Further work demonstrated a crucial role for estradiol in proplatelet formation, as evidenced by their finding that the addition of exogenous estradiol increased proplatelt form
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Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
30-Nov-2003


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