Tetrahydrogestrinone (THG) & Erythropoietin (EPO)
This is just some info I'm throwing together... people have been curious about these two alot lately, especially revolving the Barry Bonds/Marion Jones scandal... hopefully this can clear some things up....
Tetrahydrogestrinone (THG) - A designer steroid derived through chemical modification. THG set off the BALCO scandal. It was in the dirty syringe track coach Trevor Graham sent to the U.S. Anti-Doping Agency last year, and from that sample scientists created a test for it.
- `The Clear': BALCO's name for a liquid taken orally, composed of THG, and EPO (which stimulates production of red blood cells, which in turn improves endurance, SEE BELOW). BALCO founder Victor Conte said it was developed from the steroid norbolethone. Barry Bonds told a grand jury he ingested a clear substance but thought it was flaxseed oil.
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Tetrahydrogestrinone is a Potent Androgen and Progestin.
Death AK, McGrath KC, Kazlauskas R, Handelsman DJ.
Heart Research Institute, Camperdown, Sydney, New South Wales, Australia; University of Sydney; Australian Sports Drug Testing Laboratory, Australian Government Analytical Laboratories, Pymble, New South Wales; and ANZAC Research Institute, Sydney.
Tetrahydrogestrinone (THG) is a recently discovered steroid that has never been marketed and is used unlawfully to enhance sports performance. Structurally, THG resembles trenbolone, a veterinary androgen. Using a yeast-based in vitro bioassay, the investigators examined the biologic interactions of THG with the human androgen receptor (AR), progesterone receptor (PR), and estrogen receptor (ER). THG agonist activity in the AR bioassay was compared with that of gestrinone, its parent compound, the structurally similar steroid trenbolone, and nandrolone, used as a positive androgen control.THG strongly activated AR transactivation when compared with the other steroids. THG exhibited progestin activity that was 7-fold greater than that of progesterone. In contrast, gestrinone and trenbolone had much less progestin activity than progesterone. THG did not inhibit activation of the androgen receptor by testosterone or activation of the progesterone receptor by progesterone. No ER agonist or antagonist activity was observed. None of the steroids caused cellular toxicity.These findings indicate that THG is a potent androgen and progestin. It does not alter ER action and has no antagonistic effects against any of the sex steroid receptors. The discovery of this designer androgen prompts concern that a range of novel androgens might be produced from marketed progestins and other synthetic sex steroids.
PMID: 15385856
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Designer androgens in sport: when too much is never enough.
Handelsman DJ.
ANZAC Research Institute, Sydney, NSW 2139, Australia. [email protected]
The recent identification of tetrahydrogestrinone (THG), the first true "designer androgen," as a sports doping agent reflects both an alarmingly sophisticated illicit manufacturing facility and an underground network of androgen abusers in elite sports, as well as the still untapped potential for designer androgens in medicine. Never marketed, THG was apparently developed as a potent androgen that was undetectable by conventional International Olympic Committee-mandated urinary sports doping tests. As a potent androgen and progestin with unspecified contaminants, its distribution for use at high doses without any prior biological or toxicological evaluation poses significant health risks. Yet this diversion of science also highlights the prospect of designer androgens for use in human medicine. Designer androgens also offer the possibility of tissue-specific effects enhancing the beneficial effects of androgens while mitigating the undesirable ones. Further developments require better understanding of the postreceptor tissue selectivity of androgens, comparable to the mechanism underlying that of partial estrogen agonists (SERMs). This experience highlights the ongoing need for vigilance to detect novel drug doping strategies in order to maintain fairness and safety in elite sports. This will require the deployment of generic catch-all tests, such as sensitive and specific in vitro androgen bioassays, coupled with the development of mass spectrometry-based tests for specific doping agents.
PMID: 15292520
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Tetrahydrogestrinone: discovery, synthesis, and detection in urine.
Catlin DH, Sekera MH, Ahrens BD, Starcevic B, Chang YC, Hatton CK.
UCLA Olympic Analytical Laboratory, Department of Molecular and Medical Pharmacology, University of California at Los Angeles, 2122 Granville Avenue, Los Angeles, CA 90025, USA. [email protected]
Tetrahydrogestrinone (18a-homo-pregna-4,9,11-trien-17beta-ol-3-one or THG) was identified in the residue of a spent syringe that had allegedly contained an anabolic steroid undetectable by sport doping control urine tests. THG was synthesized by hydrogenation of gestrinone and characterized by mass spectrometry and NMR spectroscopy. We developed and evaluated sensitive and specific methods for rapid screening of urine samples by liquid chromatography/tandem mass spectrometry (LC/MS/MS) of underivatized THG (using transitions m/z 313 to 241 and 313 to 159) and gas chromatography/high-resolution mass spectrometry (GC/HRMS) analysis of the combination trimethylsilyl ether-oxime derivative of THG (using fragments m/z 240.14, 254.15, 267.16, and 294.19). A baboon administration study showed that THG is excreted in urine. Copyright 2004 John Wiley & Sons, Ltd.
PMID: 15174177
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FDA Warning on Unapproved Performance Enhancer
Tetrahydrogestrinone (THG), a substance taken by athletes to improve their performance, is considered to be an unapproved drug by the FDA, and cannot be legally marketed.
The FDA is warning consumers that little is known about the safety of this substance, its structure, and relationship to better-known products. The agency says that its use may pose considerable risks to health. The FDA is concerned about the marketing and use of this unapproved product and is working with other federal law enforcement agencies to aggressively "engage, enforce, and prosecute" those firms or people who manufacture, distribute, or market THG.
While in some cases THG is being represented as a dietary supplement, the FDA says that in fact the substance does not meet the definition of a dietary supplement. Rather, it is a purely synthetic "designer" steroid derived by simple chemical modification from another anabolic steroid that is explicitly banned by the United States Anti-Doping Agency, an independent body that monitors and enforces drug use restrictions in athletic competitions. THG is closely and structurally related to two other synthetic anabolic steroids, gestrinone and trenbolone. Anabolic steroids, which build muscle mass, can have serious long-term health consequences in men, women, and children.
THG cannot be legally marketed without FDA approval under the agency's rigorous approval standards, meant to ensure that drugs sold to American consumers are safe and effective.
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Erythropoietin use and abuse: When physiology and pharmacology collide.
Spivak JL.
Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
The major function of the erythrocyte is to transport oxygen from the lungs to the other tissues, a function ensured by the glycoprotein hormone erythropoietin which couples red cell production to long term tissue oxygen requirements. Tissue hypoxia is the only physiological mechanism for increasing erythropoietin production but there are a variety of mechanisms for its down regulation including hyperoxia, increased catabolism by an expanded erythroid progenitor cell pool, blood hyperviscosity independently of its oxygen content, renal disease and the cytokines produced in inflammatory, infectious and neoplastic disorders. Erythropoietin lack results in severe and often transfusion-dependent anemia but if bone marrow function is otherwise normal, recombinant human erythropoietin therapy can restore the red cell mass and alleviate the transfusion need. However, elevation of the red cell mass by recombinant human erythropoietin is associated with a reduction in plasma volume and in some patients, hypertension is induced. Elevation of the red cell mass is also associated with a reduction in cerebral blood flow. When used to gradually elevate the hematocrit to 36% in anemic patients, recombinant human erythropoietin therapy is usually uneventful. However, when the normal hematocrit level is exceeded, the risk for thrombotic events increases since blood viscosity varies exponentially with the hematocrit. Increasing the hematocrit by autologous blood transfusions can enhance athletic performance in fit individuals and recombinant human erythropoietin administration is an obvious surrogate for autologous blood transfusions. However, paradoxically, its effects are the opposite of those of endurance training, namely a change in red cell mass without an increase in the total blood volume. Thus, the use of recombinant human erythropoietin as a performance-enhancing agent is dangerous, particularly in the less fit athlete, and probably of little benefit in the highly conditioned one. Differences in the carbohydrate content of native and recombinant human erythropoietin are identifiable by isoelectric focusing, providing a direct means for detecting erythropoietin abuse using urine specimens; a panel of surrogate blood markers of enhanced erythropoiesis such as soluble transferrin receptors, serum erythropoietin, reticulocyte hematocrit and percent macrocytes provide an indirect means for this purpose. Timing of surveillance is, of course, critical due to biological limitations on the physical presence of the hormone. However, education about its dangers may prove to be the most valuable solution to abuse of recombinant human erythropoietin for competitive advantage.
PMID: 11950139
