Tetrahydrogestrinone is an
anabolic steroidAnabolic steroids, technically known as anabolic-androgen steroids or colloquially simply as "steroids", are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue ,...
developed by
Patrick ArnoldPatrick Arnold is an American organic chemist responsible for creating the designer steroid tetrahydrogestrinone, also known as THG and "the clear". THG, along with two other anabolic steroids that Patrick Arnold manufactured , were drugs at the heart of the BALCO scandal...
. It has affinity to the
androgen receptorThe androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
and the
progesterone receptorThe progesterone receptor also known as NR3C3 , is an intracellular steroid receptor that specifically binds progesterone...
, but not to the estrogen receptor. The drug has been considered a
designer drugDesigner drug is a term used to describe drugs that are created to get around existing drug laws, usually by preparing analogs or derivatives of existing drugs by modifying their chemical structure to varying degrees, or less commonly by finding drugs with entirely different chemical structures...
, closely related to the banned anabolic steroids
gestrinoneGestrinone is a synthetic steroid hormone that acts as an anti-progestin and also has some androgenic activity. It is marketed under the names Dimetriose, Dimetrose, and Nemestran, as a treatment for endometriosis. Gestrinone is available in many countries, but not in the USA...
and
trenboloneTrenbolone is a steroid used by veterinarians on livestock to increase muscle growth and appetite. To increase its effective half-life, trenbolone is not used in an unrefined form, but is rather administered as ester derivatives such as trenbolone acetate, trenbolone enanthate or trenbolone...
, and was referred to as an unapproved new drug by the
Food and Drug AdministrationThe Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) in 2003 before the subsequent scheduling of it in 2005.
Pharmacology
Structure-activity relationshipThe structure–activity relationship is the relationship between the chemical or 3D structure of a molecule and its biological activity. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism...
studies report that the potency of the drug is outstanding, surpassing, on a milligram per milligram basis, every known synthesized or commercial available
anabolic steroidAnabolic steroids, technically known as anabolic-androgen steroids or colloquially simply as "steroids", are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue ,...
at the time of its development. It is a highly potent
agonistAn agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
for the
androgenAndrogen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
and
progesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
receptors, around 10 times more potent than the comparison drugs
nandroloneNandrolone is an anabolic steroid that may be present naturally in the human body, albeit in minute quantities of less than 0.4 ng/ml. Nandrolone is most commonly sold commercially as its decanoate ester and less commonly as a phenylpropionate ester...
or
trenboloneTrenbolone is a steroid used by veterinarians on livestock to increase muscle growth and appetite. To increase its effective half-life, trenbolone is not used in an unrefined form, but is rather administered as ester derivatives such as trenbolone acetate, trenbolone enanthate or trenbolone...
, but with no
estrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
ic activity. It has been found to bind to the androgen receptor with similar affinity to
dihydrotestosteroneDihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
and produces growth of muscle tissue. According to Patrick Arnold, due the drug's potency, he never had to supply significant quantities to
BALCOBalco can refer to:* the Bay Area Laboratory Co-operative - a controversial sports medicine/nutrition centre in Burlingame, California.* Balco balcony systems who develops, designs and manufactures balcony systems and glazing solutions....
, because "just a couple of drops under the tongue" were a sufficient dose.
Method of action
When THG reaches the nucleus of a cell, it binds to the androgen receptor at the ligand-binding pocket. Here it changes the expression of a variety of genes, turning on several anabolic and androgenic functions.
It is the
ligandIn coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
’s structure which determines the number of interactions that can take place with the human androgen receptor ligand-binding domain. Even minor modifications in the ligand's structure have a great impact on the strength of the interactions this ligand has with the androgen receptor. THG, possessing a high affinity, establishes more van der Waals contacts with the receptor than with many other steroids. It is this higher affinity and specific geometry of THG which makes these interactions with the Androgen Receptor so strong, resulting in THG’s potency.
Side effects
Side effects from prolonged use are likely to include
infertilityInfertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
in both men and women, as well as other steroid side effects such as acne and
hirsutismHirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
. Unlike most other anabolic steroids, THG also binds with high affinity to the
glucocorticoidGlucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
receptor, and while this effect may cause additional weight loss, it is also likely to cause extra side effects such as
immunosuppressionImmunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
that are not seen with most other steroids.
History
For a time, THG was considered the drug of choice for safe and "invisible" world record breaking in athletics, being used by several high profile gold medal winners such as the sprinter
Marion JonesMarion Lois Jones , also known as Marion Jones-Thompson, is a former world champion track and field athlete, and a former professional basketball player for Tulsa Shock in the WNBA...
, who resigned from her athletic career in 2007 after admitting to using THG prior to the 2000 Sydney Olympics, where she had won three gold medals. It has also been used by formerly banned British athlete
Dwain ChambersDwain Anthony Chambers is an English sprinter of Afro-Caribbean descent. He has won medals on the international stage numerous times and is one of the fastest European sprinters in the history of recorded athletics. His primary event is the 100 metres sprint, in which he has the second...
and Major League Baseball first baseman
Jason GiambiJason Gilbert Giambi is an American professional baseball first baseman with the Colorado Rockies of Major League Baseball.He was the American League MVP in 2000 while with the Oakland Athletics, and is a five-time All-Star who has led the American League in walks four times, in on base percentage...
.
THG was developed by
Patrick ArnoldPatrick Arnold is an American organic chemist responsible for creating the designer steroid tetrahydrogestrinone, also known as THG and "the clear". THG, along with two other anabolic steroids that Patrick Arnold manufactured , were drugs at the heart of the BALCO scandal...
for the
Bay Area Laboratory Co-operativeThe Bay Area Laboratory Co-Operative was an American company led by founder and owner Victor Conte, a former bass player for the soul band Tower of Power. In 2003, journalists Lance Williams and Mark Fainaru-Wada investigated the company's role in a drug sports scandal later referred to as the...
(BALCO), an American nutritional supplement company. The company manufactured the drug through palladium-charcoal catalyzed hydrogenation from
gestrinoneGestrinone is a synthetic steroid hormone that acts as an anti-progestin and also has some androgenic activity. It is marketed under the names Dimetriose, Dimetrose, and Nemestran, as a treatment for endometriosis. Gestrinone is available in many countries, but not in the USA...
, a substance used in gynecology for treatment of
endometriosisEndometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
(Australian Medicines handbook 2011).
In 2003, U.S. sprint coach Trevor Graham delivered a syringe containing traces of THG to the United States Anti-Doping Agency (USADA). This helped Don Catlin, MD, the founder and then-director of the UCLA Olympic Analytical Lab, to identify and develop a test for THG, the second reported designer anabolic steroid.
See also
- Bay Area Laboratory Co-operative
The Bay Area Laboratory Co-Operative was an American company led by founder and owner Victor Conte, a former bass player for the soul band Tower of Power. In 2003, journalists Lance Williams and Mark Fainaru-Wada investigated the company's role in a drug sports scandal later referred to as the...
- Marion Jones
Marion Lois Jones , also known as Marion Jones-Thompson, is a former world champion track and field athlete, and a former professional basketball player for Tulsa Shock in the WNBA...
- Barry Bonds
Barry Lamar Bonds is an American former Major League Baseball outfielder. Bonds played from 1986 to 2007, for the Pittsburgh Pirates and San Francisco Giants. He is the son of former major league All-Star Bobby Bonds...
- Norbolethone
Norbolethone is an anabolic steroid. It was first developed in 1966 by Wyeth Laboratories, and tested for use as an agent to encourage weight gain and for the treatment of short stature, but was never marketed commercially because of fears that it might be toxic...
- Jason Giambi
Jason Gilbert Giambi is an American professional baseball first baseman with the Colorado Rockies of Major League Baseball.He was the American League MVP in 2000 while with the Oakland Athletics, and is a five-time All-Star who has led the American League in walks four times, in on base percentage...
External links