Ecdysterone

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A steroid hormone that regulates the processes of MOLTING or ecdysis in insects. Ecdysterone is the 20-hydroxylated ECDYSONE.

20-Hydroxyecdysone (ecdysterone or 20E) 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.

General Properties

*Molecular Weight

480.63

*Molecular Formula

C₂₇H₄₄O₇

*IUPAC NAME

(2S,3R,5R,9R,10R,13R,14S,17S)-2,3,14-trihydroxy-10,13-dimethyl-17-[(2R,3R)-2,3,6-trihydroxy-6-methylheptan-2-yl]-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one

*Canonical Smiles

CC12CCC3C(=CC(=O)C4C3(CC(C(C4)O)O)C)C1(CCC2C(C)(C(CCC(C)(C)O)O)O)O

*Isomeric Smiles

C[C@]12CC[C@H]3C(=CC(=O)[C@H]4[C@@]3(C[C@@H]([C@@H](C4)O)O)C)[C@@]1(CC[C@@H]2[C@](C)([C@@H](CCC(C)(C)O)O)O)O

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.<ref>C. S. Thummel & J. Chory (2002). Steroid signaling in plants and insects — common themes, different pathways. Genes and Development 16: 3113–3129. doi:10.1101/gad.1042102. PMID 12502734. </ref> 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.<ref>A. M. Handler (1982). Ecdysteroid titers during pupal and adult development in Drosophila melanogaster. Developmental Biology 93 (1): 73–82. doi:10.1016/0012-1606(82)90240-8. </ref> 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.

Ecdysteroid activity in arthropods

Ecdysteroid 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 humans and other mammals

Consumption

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, 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 <ref>Chermnykh, N.S., et.al. (1988). The action of methandrostenolone and ecdysterone on the physical endurance of animals and on protein metabolism in the skeletal muscles. Farmakol Toksikol (USSR) 51 (6): 57–60. PMID 3234543. </ref><ref>Simakin, S. Yu., et al. (1988). The Combined Use of Ecdisten and the Product 'Bodrost' during Training in Cyclical Types of Sport. Scientific Sports Bulletin (2). </ref>. 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.Template:Fact 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 <ref>D. S. Trenin & V. V. Volodin (1999). 20-hydroxyecdysone as a human lymphocyte and neutrophil modulator: in vitro evaluation. Archives of Insect Biochemistry and Physiology 41 (3): 156–161. doi:10.1002/(SICI)1520-6327(1999)41:3<156::AID-ARCH7>3.0.CO;2-Q. </ref>.

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".<ref> Lafont, R. & Dinan, L. (2003) Practical uses for ecdysteroids in mammals including humans: an update. J. Insect Sci. 3:7 Full-text</ref>

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.

Research tool

20E (and other ecdysteroids) are used in biochemistry research as inducers 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<ref>E. Saez, M. C. Nelson, B. Eshelman, E. Banayo, A. Koder, G. J. Cho & R. M. Evans (2000). Identification of ligands and coligands for the ecdysone-regulated gene switch. Proceedings of the National Academy of Science 97 (26): 14512–14517. doi:10.1073/pnas.260499497. </ref>. 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)<ref>Graham, L.D. (2002) Ecdysone-controlled expression of transgenes. Expert Opin. Biol. Ther. 2 (5), 525-535.</ref>.

External Links

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