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Why Is HGH So Hard To Detect?Doesn't it come out in your pee?

By Daniel Engber
Posted Thursday, June 8, 2006, at 6:29 PM ET

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On Tuesday, federal agents raided the home of Arizona Diamondbacks pitcher Jason Grimsley as part of a drug investigation. The government says Grimsley received two growth hormone "kits" in the mail in April. Major League Baseball has banned the use of human growth hormone, but some experts say there's no reliable test for the drug. Why not?

Lab-produced growth hormone looks almost exactly like the stuff we make in our bodies. It has the same sequence of amino acids, and it stays in the bloodstream for the same amount of time. (Doctors used to collect doses of growth hormone from the pituitary glands of corpses. The practice halted after it was linked to the spread of Creutzfeldt-Jakob disease.) It's much easier to suss out a steroid user; synthetic steroids don't have the same structure as their natural kin.*

One approach to testing makes use of the fact that growth hormone can vary in size. The body makes different forms of GH, each of which has a unique molecular weight (measured in daltons). Most natural (or "endogenous") growth hormone comes in either a 22,000- or a 20,000-dalton form. Synthetic growth hormone, on the other hand, tends to come in a standard size: 22,000 daltons. By checking the ratio of the 22-kDa and 20-kDa varieties, it's possible spot the presence of the lab-made chemical. Olympic athletes at Athens and Turin were tested for unnatural growth hormone using just this test.


The ratio test has two big problems. First, you have to catch the doper pretty soon after he takes the drug—the ratio of the two isoforms returns to normal within a few days. Anti-doping experts are hard at work to find a more persistent marker for synthetic-hormone use. One approach would be to look for another protein whose levels are affected by an increase in growth hormone. These might be other compounds related to growth, like the insulinlike growth factors, or IGFs.

The second problem with the ratio test is the needle. Players are more willing to pee in a cup than to pop a vein, but you won't find much growth hormone in a sample of urine. Urinalysis works for steroids because they're much smaller molecules—on the order of hundreds of daltons, as opposed to tens of thousands. The kidneys pass anabolic steroids into the urine, but they leave out almost all of the larger growth hormone. (Researchers financed by Major League Baseball are looking into the possibility of a urine test for growth hormone.)

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Explainer thanks Don Very of the Institute for Bioanalytics.

Correction, June 9, 2006: This piece originally stated that synthetic steroids don't share the same sequence with naturally produced steroids. Since the steroids in question aren't made of chains of amino acids like proteins, they don't have a "sequence," per se. It's more accurate to say that synthetic steroids have a different structure than naturally produced steroids. (Return to the corrected sentence.)

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Daniel Engber is an associate editor at Slate. He can be reached at .
Photograph of Jason Grimsley on the Slate home page by Mark Goldman/Icon SMI.
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