20-hydroxyecdysone
Encyclopedia
20-Hydroxyecdysone is a naturally occurring ecdysteroid
hormone
which controls the ecdysis
(moulting) and metamorphosis
of arthropods. It is therefore one of the most common moulting hormones in insects, crabs, etc. It is also a phytoecdysteroid
produced by various plants, including Cyanotis vaga, where its purpose is presumably to disrupt the development
and reproduction of insect pests. In arthropods, 20E acts through the ecdysone receptor
. Although mammals lack this receptor
, 20E does appear to affect mammalian (including human
) physiology
, but there is disagreement over the details of its effects. 20E is an ingredient of some preparations that aim to enhance physical performance.
, 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 the ecdysone receptor
throughout development, possibility indicating a functional feedback mechanism.
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-hydroxyecdysone (20E) regulate 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. Indeed, the main receptor of these hormone signals - the ecdysone receptor
- is an intracellular
protein
.
in sport
and bodybuilding
.
Despite lacking FDA
approval, 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.
There is also 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 .
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".
Clearly, more research is needed to determine the significance of the effects of 20-hydroxyecdysone in mammals and how they affect the safety profile of 20-hydroxyecdysone when it is taken as a dietary supplement by humans. 20-hydroxyecdysone is still considered a steroid "hormone" and may cause side effects that normal steroids produce.
A comprehensive study, designed to find any strength or athletic improvement from 20-Hydroxyecdysone was published in 2006. The study looked for improvement in actual exercises performed and tested for improvements/increases in chemical indicators such as body composition and free/available testosterone. The study concluded supplementation or 200mg per day had no effect on the individuals in the study.
s in transgenic animals, whereby if you put a new gene into an animal so that its expression is under the control of an introduced ecdysone receptor
, then adding or removing 20-hydroxyecdysone from the animal's diet gives a convenient way to turn the inserted gene on or off (see Ecdysone receptor
). At usual doses, 20-hydroxyecdysone appears to have little or no effect on animals that do not have extra genes inserted; it also 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).
Ecdysteroid
Ecdysteroids are insect moulting and sex hormones which include ecdysone and its homologues such as 20-hydroxyecdysone. Ecdysteroids also occur in other invertebrates where they can play a different role. They also appear in many plants mostly as a protection agents against herbivore insects...
hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
which controls the ecdysis
Ecdysis
Ecdysis is the moulting of the cuticula in many invertebrates. This process of moulting is the defining feature of the clade Ecdysozoa, comprising the arthropods, nematodes, velvet worms, horsehair worms, rotifers, tardigrades and Cephalorhyncha...
(moulting) and metamorphosis
Metamorphosis
Metamorphosis is a biological process by which an animal physically develops after birth or hatching, involving a conspicuous and relatively abrupt change in the animal's body structure through cell growth and differentiation...
of arthropods. It is therefore one of the most common moulting hormones in insects, crabs, etc. It is also a phytoecdysteroid
Phytoecdysteroid
Phytoecdysteroids are plant derived ecdysteroids. Phytoecdysteroids are a class of chemicals that plants synthesize for defense against phytophagous insects. These compounds are exact replicas of hormones used by the arthropod and crustacean families in the molting process known as ecdysis...
produced by various plants, including Cyanotis vaga, where its purpose is presumably to disrupt the development
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
and reproduction of insect pests. In arthropods, 20E acts through the ecdysone receptor
Ecdysone receptor
The ecdysone receptor is a nuclear receptor found in arthropods, where it controls development and contributes to other processes such as reproduction. The receptor is a non-covalent heterodimer of two proteins, the EcR protein and ultraspiracle protein . It binds to and is activated by ecdysteroids...
. Although mammals lack this receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
, 20E does appear to affect mammalian (including human
Human
Humans are the only living species in the Homo genus...
) physiology
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
, but there is disagreement over the details of its effects. 20E is an ingredient of some preparations that aim to enhance physical performance.
Sources of 20E in arthropods
The primary sources of 20E in larvae are the prothoracic glandProthoracic gland
The prothoracic glands are either of a pair of endocrine glands located in the prothorax of certain insects and regulating molting. They have a ectodermal origin and secrete ecdysteroids, such as ecdysone and 20-hydroxyecdysone....
, ring gland, gut, and fat bodies. These tissues convert dietary cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
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 the ecdysone receptor
Ecdysone receptor
The ecdysone receptor is a nuclear receptor found in arthropods, where it controls development and contributes to other processes such as reproduction. The receptor is a non-covalent heterodimer of two proteins, the EcR protein and ultraspiracle protein . It binds to and is activated by ecdysteroids...
throughout development, possibility indicating a functional feedback mechanism.
Ecdysteroid activity in arthropods
EcdysteroidEcdysteroid
Ecdysteroids are insect moulting and sex hormones which include ecdysone and its homologues such as 20-hydroxyecdysone. Ecdysteroids also occur in other invertebrates where they can play a different role. They also appear in many plants mostly as a protection agents against herbivore insects...
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
Ecdysone
Ecdysone is a steroidal prohormone of the major insect molting hormone 20-hydroxyecdysone, which is secreted from the prothoracic glands. Insect molting hormones are generally called ecdysteroids. Ecdysteroids act as moulting hormones of arthropods but also occur in other related phyla where they...
and 20-hydroxyecdysone (20E) regulate 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. Indeed, the main receptor of these hormone signals - the ecdysone receptor
Ecdysone receptor
The ecdysone receptor is a nuclear receptor found in arthropods, where it controls development and contributes to other processes such as reproduction. The receptor is a non-covalent heterodimer of two proteins, the EcR protein and ultraspiracle protein . It binds to and is activated by ecdysteroids...
- is an intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
.
Use as Supplement
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 cost-effectively. This has led to experimentation with its use as an anabolic steroidAnabolic steroid
Anabolic 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 ,...
in sport
Sport
A Sport is all forms of physical activity which, through casual or organised participation, aim to use, maintain or improve physical fitness and provide entertainment to participants. Sport may be competitive, where a winner or winners can be identified by objective means, and may require a degree...
and bodybuilding
Bodybuilding
Bodybuilding is a form of body modification involving intensive muscle hypertrophy. An individual who engages in this activity is referred to as a bodybuilder. In competitive and professional bodybuilding, bodybuilders display their physiques to a panel of judges, who assign points based on their...
.
Despite lacking FDA
Food and Drug Administration
The 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...
approval, 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
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
and DHT
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
production, and include androgenic changes in females such as growth of facial and body hair and deepening of the voice, as well as gastrointestinal
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
problems for both sexes, such as nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, bloating
Bloating
Bloating is any abnormal general swelling, or increase in diameter of the abdominal area. As a symptom, the patient feels a full and tight abdomen, which may cause abdominal pain sometimes accompanied by increased borborygmus or more seriously the total lack of borborygmus.-Symptoms:The most common...
, and diarrhoea. Clinical studies by ICN Pharmaceuticals
Valeant Pharmaceuticals International
Valeant Pharmaceuticals International, Inc. is a pharmaceutical company with activities spanning the drug discovery pipeline from target identification through clinical trials and commercialization. The focus of the company is on neurology, dermatology and infectious disease with several drugs in...
demonstrated that the results are further improved when the drug is combined with a high-protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
diet, to the point of equaling or even surpassing the beneficial effects of conventionally derived steroids such as Dianabol
Methandrostenolone
Methandrostenolone is an orally-effective anabolic steroid originally developed by John Ziegler and released in the US in the early 1960s by Ciba. It was used as an aid to muscle growth by bodybuilders until its ban by Congress under the Controlled Substances Act...
. 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.
There is also 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 .
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".
Clearly, more research is needed to determine the significance of the effects of 20-hydroxyecdysone in mammals and how they affect the safety profile of 20-hydroxyecdysone when it is taken as a dietary supplement by humans. 20-hydroxyecdysone is still considered a steroid "hormone" and may cause side effects that normal steroids produce.
A comprehensive study, designed to find any strength or athletic improvement from 20-Hydroxyecdysone was published in 2006. The study looked for improvement in actual exercises performed and tested for improvements/increases in chemical indicators such as body composition and free/available testosterone. The study concluded supplementation or 200mg per day had no effect on the individuals in the study.
Use as Research tool
20E (and other ecdysteroids) are used in biochemistry research as inducerInducer
In molecular biology, an inducer is a molecule that starts gene expression.For a gene to be expressed, its DNA sequence must be copied to make a smaller, mobile molecule called messenger RNA , which carries the instructions for making a protein to the site where the protein is manufactured...
s in transgenic animals, whereby if you put a new gene into an animal so that its expression is under the control of an introduced ecdysone receptor
Ecdysone receptor
The ecdysone receptor is a nuclear receptor found in arthropods, where it controls development and contributes to other processes such as reproduction. The receptor is a non-covalent heterodimer of two proteins, the EcR protein and ultraspiracle protein . It binds to and is activated by ecdysteroids...
, then adding or removing 20-hydroxyecdysone from the animal's diet gives a convenient way to turn the inserted gene on or off (see Ecdysone receptor
Ecdysone receptor
The ecdysone receptor is a nuclear receptor found in arthropods, where it controls development and contributes to other processes such as reproduction. The receptor is a non-covalent heterodimer of two proteins, the EcR protein and ultraspiracle protein . It binds to and is activated by ecdysteroids...
). At usual doses, 20-hydroxyecdysone appears to have little or no effect on animals that do not have extra genes inserted; it also 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
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
, it may be necessary to investigate more thoroughly the natural sources of ecdysteroids in humans (which appear to include dietary phytoecdysteroids, gut flora
Gut flora
Gut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora....
, helminth infections, and other diseases).