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Estrogen Steps Up to the Platelet

4 December 2003 (All day)
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More platelets, please. Estrogen may prompt megakaryocyte cells to boost platelet formation.

Estrogen is best known for its starring role in running the female reproductive system. Now, researchers in Japan think they've uncovered a new role for it in maintaining healthy blood in both sexes. They argue that estrogen might have potential for treating blood diseases such as leukemia and anemia.

The hormone may be necessary for the production of blood platelets, according to a study in the 1 December issue of Genes and Development. Up to a trillion platelets reside in an adult's blood. By causing clotting at wounds, they are essential in stemming bleeding. Platelets are made by enormous megakaryocyte cells in bone marrow. These cells extend beaded strings of cytoplasm known as proplatelets, which break, releasing up to thousands of platelets.

Understanding platelet formation has important clinical implications; too many platelets can cause excessive clotting, whereas too few increases the risk of fatal bleeding. It's clear that a gene called p45-Nfe2 turns on and off some of the genes involved, but researchers have struggled to work out the entire chain of events. Now, cell biologist Yuka Nagata of the Institute of Physical and Chemical Research (RIKEN) in Saitama, Japan, and her team think they may have filled in the gaps.

The scientists first compared mouse megakaryocyte cells created from embryonic stem cells engineered to lack p45-Nfe2 with normal megakaryocytes. To their surprise, a gene called 3beta-HSD, which plays a role in synthesis of steroid hormones, was less active in the experimental cells. In normal megakaryocytes, 3beta-HSD boosts production of estradiol, the most common form of estrogen. The new finding suggests that p45-Nfe2 stimulates 3beta-HSD to produce estrogen, which in turn hikes platelet production. Indeed, another experiment in live mice showed that the estrogen-blocking drug tamoxifen slashed platelet counts by 45% within 9 days.

Patients suffering from low-platelet-count diseases such as bone marrow abnormalities or those undergoing chemotherapy may benefit from treatment with estradiol, Nagata says. Conversely, patients with high platelet counts, prone to strokes and heart attacks, might be candidates for estrogen-blocking drugs, she says.

This work has "uncovered an important piece of the puzzle" of how platelets form, says oncologist and developmental biologist Ramesh Shivdasani of Harvard Medical School in Boston, Massachusetts. Other genes are certainly also involved, he says. The next step, adds hematologist Ken Kaushansky of the University of California, San Diego, is to figure out exactly how estrogen leads to more platelets. However, the side effects of estrogen could hinder wide use as a treatment for platelet abnormalities, he warns.

Related sites
A video of proplatelet formation
Background information on platelet formation

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