20-Hydroxyecdysone

Ecdysterone
(2β,3β,5β,22R)-2,3,14,20,22,25- hexahydroxycholest-7-en-6-one
CAS number 5289-74-7	ATC code
Chemical formula	C27H44O7
Molecular weight	480.634
Bioavailability	?%
Metabolism	Hepatic
Elimination half-life	? hours
Excretion	Urinary:?%
Pregnancy category	X
Legal status	Undetermined
Routes of administration	Oral

20-hydroxyecdysone (ecdysterone or 20-E) is a naturally occurring ecdysteroid hormone produced by various plants including Cyanotis vaga. Upon its isolation, it quickly became apparent that it was taken up by insects feeding on the plant, and played a key role in cell proliferation, growth and apoptosis by controlling gene expression involved in ecdysis and metamorphosis. It is one of the most common moulting hormones in insects, crabs, and some worms and can disrupt their moulting and reproduction. It has been suggested as a disruptor to avian influenza which can be transmitted through such vectors. It acts through a heterodimeric receptor comprising the ecdysone receptor and the ultraspiracle proteins (USP) to cause a positive nitrogen balance in the body.

Sources of 20E in arthropods

The primary sources of 20E in larvae are the prothoracic gland, ring gland, gut, and fat bodies. These tissues convert dietary cholesterol into the mature forms of the hormone 20E . For the most part these glandular tissues are lost in the adult with exception of the fat body, which is retained as a sheath of lipid tissue surrounding the brain and organs of the abdomen. In the adult female the ovary is a substantial source of 20E production . Adult males are left with, so far as is currently known, one source of 20E which is the fat body tissue. These hormone producing tissues express both EcR and USP throughout development possibility indicating a functional feedback mechanism.

Ecdysteroid Activity in Arthropods

Ecdysteroids is a term used to describe a group of steroid hormones in insects that are derived from enzymatic modification of cholesterol by p450 enzymes. This occurs by a mechanism similar to steroid synthesis in vertebrates. Ecdysone and 20-alphahydroxy ecdysone (20E) regulated larval molts, onset of puparium formation, and metamorphosis. Being that these hormones are hydrophobic, they traverse lipid membranes and permeate the tissues of an organism. A crucial receptor of these hormone signals are the Ecdysone Receptor (EcR) proteins. These proteins are nuclear hormone receptors (NHR)that directly modify gene transcription. These proteins form heterodimers with another NHR ultraspiracle (USP), which is the invertebrate ortholog of Retinoid X receptor (RXR). This heterodimer binds to Ecdysone Responsive Elements (EcRE) and waits for ligand binding. Only tissues expressing EcR will be responsive to ecdysone or 20E.

In humans

When first isolated, there was little interest from the commercial sector due to the lack of a cost-effective way to extract or synthesize the chemical. However, recent breakthroughs have meant that it can now be isolated in an extremely concentrated form. This has led to experimentation with its use as an anabolic steroid in sport and bodybuilding.

Despite lacking FDA approval and being largely illegal in the West, it has proven to be moderately successful as a commercial product in the countries in which it is produced, likely due to its efficacy in promoting muscle growth and fat loss, and lower frequency of side-effects usually associated with anabolic steroids. Such side effects are still fairly common, however, as a result of increased testosterone and DHT production, and include androgenic changes in females such as growth of facial and body hair and deepening of the voice, as well as gastrointestinal problems for both sexes, such as nausea, bloating, and diarrhoea. Clinical studies by ICN Pharmaceuticals demonstrated that the results are further improved when the drug is combined with a high-protein diet, to the point of equaling or even surpassing the beneficial effects of conventionally derived steroids such as Dianabol . The same studies showed the effective dose for a human to be around 5 mg per kg of body mass, daily. The compound becomes toxic only at doses of 6400 mg per kg of body mass per day.

In addition to its potential use as an anabolic growth hormone, 20-hydroxyecdysone has proven to cause moderate increases in testosterone production in males. This has led to speculation and a small number of partially successful trials in testing its use in improving overall sexual function.

An academic review published in 2003 concluded that "The impressive development of preparations containing ecdysteroids suggests that this class of molecule has indeed at least some of the claimed effects. The scientific justification for such commercial developments relies, however, on just a few references (ca. 10), often with the same ones being cited to support quite different effects".

It is unclear whether 20-hydroxyecdysone actually has any effect on humans. It is used widely in biochemistry research as a transcription promoter in transgenic animals, whereby if you put a new gene into an animal with a promoter sequence that is activated by 20-hydroxyecdysone, then adding or removing 20-hydroxyecdysone from the animals diet gives a convenient way to turn the inserted gene on or off. 20-hydroxyecdysone appears to have little or no effect on animals that do not have extra genes inserted and has high bioavailability when taken orally, so it is useful for determining whether the transgene has been taken up effectively;. For uses in gene therapy, it may be necessary to investigate more thoroughly the natural sources of ecdysteroids in humans (which appear to include dietary phytoecdysteroids, gut flora, helminth infections, and other diseases).

However there is some evidence to show that 20-hydroxyecdysone has effects on some kinds of blood cells such as lymphocytes and neutrophils, and may act as an immunomodulator . More research is needed to determine the significance of these effects and how they affect the safety profile of 20-hydroxyecdysone when it is taken as a supplement by humans.

20-hydroxyecdysone is still considered a steroid "hormone" and may cause side effects that normal steroids produce.

Any types of supplements containing 20-hydroxyecdysone should not be taken by anyone under the age of 18.