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Sex hormone controls blood stem cells, researchers show

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By Anette Breindl
Science Editor

Sex organs are controlled by sex hormones, to nobody’s surprise – that’s their point.

But now, researchers have shown that blood, too, is affected by sex hormones. Blood-forming stem cells in male and female mice differ in their abilities to divide and their response to estrogen, presumably to allow females to cope with the blood-forming demands of pregnancy and childbirth.

They published their findings in the Jan. 23, 2014, advance online issue of Nature.

As surprising as they are, the findings had to some degree been hiding in plain sight.

Senior author Sean Morrison told BioWorld Today that his team had noticed high variability in their studies of blood stem cells “for years . . . but no one had picked up on the fact that the variability correlated with the sex of the mouse.

“It’s kind of remarkable,” he added, “that no one has seen this before.”

Morrison, who is at the University of Texas Southwestern Medical School’s Children’s Medical Research Center, and his team looked at the effects of estrogen on blood stem cells as part of a larger effort to look at systemwide regulation of stem cells.

Part of the reason no one had noticed estrogen’s effects on blood stem cells, he contended, is that “there’s been a tendency in stem cell biology to focus on local regulation.”

But he argued that it’s important for the local authorities to know what the rest of the organism is doing.

“If, for example, your body is starving, all of your tissues need to know that, so that they don’t embark on major remodeling of a tissue or organ while you don’t have the energy for it.”

Likewise, in women, “all of your tissues need to know you’re pregnant – it’s a whole-body experience.”

In their experiments, Morrison and his colleagues showed that both male and female blood stem cells express estrogen receptors, and that treating males as well as females with estrogen stimulated the stem cells to divide more frequently and produce more red blood cells. Genetically deleting the estrogen receptor from blood stem cells left them insensitive to estrogen, showing that the effect was a direct one.

Morrison stressed that neither his team nor anyone else has demonstrated estrogen’s effects on blood-forming stem cells in humans, and that such an effect would be hard to test directly, because the most direct way of seeing an effect would involve repeated biopsies of the bone marrow.

But if the same effects do occur in humans, the findings “could have pretty broad implications, at least for young women that still have high estrogen levels.”

He noted that the toxicity of chemotherapy and radiation damage dividing cells, and blood stem cells are one major category of cells affected by such treatments.

It might be useful to either take estrogen levels – which fluctuate with the menstrual cycle and are four times as high shortly before as after ovulation – into account, or to treat women with an estrogen inhibitor before chemotherapy to minimize stem cell activity during treatment. Conversely, estrogen might be used to stimulate the production of red blood cells.

The findings open up the possibility that some blood cancers are fueled by estrogen in the same way that many breast cancers are – a possibility that, if it turns out to be true, would suggest that such cancers might benefit from the same estrogen blockers that are used to treat those breast cancers.

“There’s a lot of things we’d like to test now,” Morrison said. For the time being, those tests will be in mice. But ultimately, he said, “there are numerous clinical opportunities to pursue.”