20-Hydroxyecdysone

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20-Hydroxyecdysone
20-Hydroxyecdysone.svg
20-Hydroxyecdysone 3D ball.png
Clinical data
Pregnancy
category
  • X
Routes of
administration 		Oral
Legal status
Legal status
Pharmacokinetic data
Metabolism Hepatic
Elimination half-life 4-9 hours
Excretion Urinary:?%
Identifiers
  • (2β,3β,5β,22R)-2,3,14,20,22,25-Hexahydroxycholest-7-en-6-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.241.312 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C27H44O7
Molar mass 480.642 g·mol−1
3D model (JSmol)
  • O=C1\C=C3/[C@@H]([C@]2(C[C@H](O)[C@H](O)C[C@@H]12)C)CC[C@]4([C@@]3(O)CC[C@@H]4[C@](O)(C)[C@H](O)CCC(O)(C)C)C
  • InChI=1S/C27H44O7/c1-23(2,32)9-8-22(31)26(5,33)21-7-11-27(34)16-12-18(28)17-13-19(29)20(30)14-24(17,3)15(16)6-10-25(21,27)4/h12,15,17,19-22,29-34H,6-11,13-14H2,1-5H3/t15-,17-,19+,20-,21-,22+,24+,25+,26+,27+/m0/s1 Yes check.svgY
  • Key:NKDFYOWSKOHCCO-YPVLXUMRSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 , Ajuga turkestanica and Rhaponticum carthamoides where its purpose is presumably to disrupt the development and reproduction of insect pests. In arthropods, 20-hydroxyecdysone acts through the ecdysone receptor. Although mammals lack this receptor, 20-hydroxyecdysone affects mammalian biological systems. 20-Hydroxyecdysone is an ingredient of some supplements that aim to enhance physical performance. In humans, it is hypothesized to bind to the estrogen receptor beta (ERβ) protein-coding gene. [1]

Contents

Sources in arthropods

The primary sources of 20-hydroxyecdysone in larvae are the prothoracic gland, ring gland, gut, and fat bodies. These tissues convert dietary cholesterol into the mature forms of the hormone 20-hydroxyecdysone. [2] 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 20-hydroxyecdysone production. [3] Adult males are left with, so far as is currently known, one source of 20-hydroxyecdysone which is the fat body tissue. These hormone producing tissues express the ecdysone receptor throughout development, possibly indicating a functional feedback mechanism.

Ecdysteroid activity in arthropods

An ecdysteroid is a type 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 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

Use as supplement

20-Hydroxyecdysone and other ecdysteroids are marketed as ingredients in nutritional supplements for various sports, particularly bodybuilding. [4] A 2006 study looked for improvement in actual exercises performed and tested for improvements/increases in chemical indicators such as body composition and free/available testosterone and concluded that using 30 mg per day of 20-hydroxyecdysone administered orally did not significantly affect anabolic or catabolic responses to resistance training, body composition, or training adaptations. [5] However, a number of earlier studies supported the anabolic effects of 20-Hydroxyecdysone. [6] [7] [8] [9] [10] [11] A more recent study conducted in 2019 by a team that included the Department for Molecular and Cellular Sports Medicine at the German Sport University Cologne, found that significantly higher increases in muscle mass were observed in participants dosed with ecdysterone, with significantly more pronounced increases in one-repetition bench press performance. [12] The study was funded by the World Anti-Doping Agency (WADA) and demonstrated a significant dose-responsive anabolic effect of 20-Hydroxyecdysone supplementation on athletes during resistance training. Furthermore, recent studies have elucidated that the mechanism of action of 20-Hydroxyecdysone on human muscle cells is relatively selective activation of the beta form of the estrogen receptor (ERβ), [13] which is known to result in muscle hypertrophy. [14] [ promotional source? ]

Use as research tool

20-Hydroxyecdysone and other ecdysteroids are used in biochemistry research as inducers in transgenic animals, whereby a new gene is introduced into an animal so that its expression is under the control of an introduced ecdysone receptor. Adding or removing ecdysteroids from the animal's diet then 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. [15]

Related Research Articles

<span class="mw-page-title-main">Ecdysone</span> Precursor of an insect hormone

Ecdysone is a prohormone of the major insect molting hormone 20-hydroxyecdysone, secreted from the prothoracic glands. It is of steroidal structure. Insect molting hormones are generally called ecdysteroids. Ecdysteroids act as moulting hormones of arthropods but also occur in other related phyla where they can play different roles. In Drosophila melanogaster, an increase in ecdysone concentration induces the expression of genes coding for proteins that the larva requires. It causes chromosome puffs to form in polytene chromosomes. Recent findings in the laboratory of Chris Q. Doe have found a novel role of this hormone in regulating temporal gene transitions within neural stem cells of the fruit fly.

<span class="mw-page-title-main">Androstenedione</span> Endogenous weak androgen

Androstenedione, or 4-androstenedione, also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepiandrosterone (DHEA). It is closely related to androstenediol (androst-5-ene-3β,17β-diol).

Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone receptors are members of the nuclear receptor subfamily 3 (NR3) that include receptors for estrogen and 3-ketosteroids. In addition to nuclear receptors, several G protein-coupled receptors and ion channels act as cell surface receptors for certain steroid hormones.

<span class="mw-page-title-main">Selective estrogen receptor modulator</span> Drugs acting on the estrogen receptor

Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.

<span class="mw-page-title-main">Estrogen receptor</span> Proteins activated by the hormone estrogen

Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors, which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs), which are mostly G protein-coupled receptors. This article refers to the former (ER).

<span class="mw-page-title-main">Gidazepam</span> Benzodiazepine medication

Gidazepam, also known as hydazepam or hidazepam, is a drug which is an atypical benzodiazepine derivative, developed in the Soviet Union. It is a selectively anxiolytic benzodiazepine. It also has therapeutic value in the management of certain cardiovascular disorders.

<span class="mw-page-title-main">Trenbolone acetate</span> Chemical compound

Trenbolone acetate, sold under brand names such as Finajet and Finaplix among others, is an androgen and anabolic steroid (AAS) medication which is used in veterinary medicine, specifically to increase the profitability of livestock by promoting muscle growth in cattle. It is given by injection into muscle.

<span class="mw-page-title-main">Ecdysteroid</span> Group of steroid hormones

Ecdysteroids are arthropod steroid hormones that are mainly responsible for molting, development and, to a lesser extent, reproduction; examples of ecdysteroids include ecdysone, ecdysterone, turkesterone and 2-deoxyecdysone. These compounds are synthesized in arthropods from dietary cholesterol upon metabolism by the Halloween family of cytochrome P450s. Phytoecdysteroids also appear in many plants mostly as a protection agents against herbivore insects.

<span class="mw-page-title-main">Selective androgen receptor modulator</span> Class of pharmaceutical drugs

Selective androgen receptor modulators (SARMs) are a class of drugs that selectively activate the androgen receptor in specific tissues, promoting muscle and bone growth while having less effect on male reproductive tissues like the prostate gland.

<span class="mw-page-title-main">Estrogen receptor beta</span> Protein-coding gene in the species Homo sapiens

Estrogen receptor beta (ERβ) also known as NR3A2 is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by the ESR2 gene.

<span class="mw-page-title-main">Ecdysone receptor</span>

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 (USP). It binds to and is activated by ecdysteroids. Insect ecdysone receptors are currently better characterized than those from other arthropods, and mimics of ecdysteroids are used commercially as caterpillar-selective insecticides.

<span class="mw-page-title-main">Anabolic steroid</span> Steroidal androgen that is structurally related and has similar effects to testosterone

Anabolic steroids, also known as anabolic-androgenic steroids (AAS), are a class of drugs that are structurally related to testosterone, the main male sex hormone, and produce effects by binding to the androgen receptor. Anabolic steroids have a number of medical uses, but are also used by athletes to increase muscle size, strength, and performance.

<span class="mw-page-title-main">Enobosarm</span> Investigational selective androgen receptor modulator

Enobosarm, also formerly known as ostarine and by the developmental code names GTx-024, MK-2866, and S-22, is a selective androgen receptor modulator (SARM) which is under development for the treatment of androgen receptor-positive breast cancer in women and for improvement of body composition in people taking GLP-1 receptor agonists like semaglutide. It was also under development for a variety of other indications, including treatment of cachexia, Duchenne muscular dystrophy, muscle atrophy or sarcopenia, and stress urinary incontinence, but development for all other uses has been discontinued. Enobosarm was evaluated for the treatment of muscle wasting related to cancer in late-stage clinical trials, and the drug improved lean body mass in these trials, but it was not effective in improving muscle strength. As a result, enobosarm was not approved and development for this use was terminated. Enobosarm is taken by mouth.

<span class="mw-page-title-main">Halloween genes</span> Set of genes that influence embryonic development

The halloween genes are a set of genes identified in Drosophila melanogaster that influence embryonic development. All of the genes code for cytochrome P450 enzymes in the ecdysteroidogenic pathway (biosynthesis of ecdysone from cholesterol). Ecdysteroids such as 20-hydroxyecdysone and ecdysone influence many of the morphological, physiological, biochemical changes that occur during molting in insects.

<span class="mw-page-title-main">Fabomotizole</span> Anxiolytic drug

Fabomotizole is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions. Its mechanism of action remains poorly defined however, with GABAergic, NGF- and BDNF-release-promoting, MT1 receptor agonism, MT3 receptor antagonism, and sigma agonism suggested as potential mechanisms. Fabomotizole was shown to inhibit MAO-A reversibly and there might be also some involvement with serotonin receptors. Clinical trials have shown fabomotizole to be well tolerated and reasonably effective for the treatment of anxiety.

<span class="mw-page-title-main">3β-Androstanediol</span> Chemical compound

3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, and sometimes shortened in the literature to 3β-diol, is an endogenous steroid hormone and a metabolite of androgens like dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT).

<span class="mw-page-title-main">Trenbolone enanthate</span> Chemical compound

Trenbolone enanthate, known by the nickname Trenabol, is a synthetic and injected anabolic–androgenic steroid (AAS) and a derivative of nandrolone which was never marketed. It is the C17β enanthate ester and a long-acting prodrug of trenbolone. Trenbolone enanthate was never approved for medical or veterinary use but is used in scientific research and has been sold on the internet black market as a designer steroid for bodybuilders and athletes.

<span class="mw-page-title-main">8β-VE2</span> Chemical compound

8β-VE2, or 8β-vinylestradiol, also known as 8β-vinylestra-1,3,5(10)-triene-3β,17β-diol, is a synthetic estrogen featuring an estradiol core. It is a highly potent and selective agonist of the ERβ that is used in scientific research to study the function of the ERβ. It has 190-fold higher potency in transactivation assays of the ERβ relative to the ERα and 93- (rat) and 180-fold (human) preference in binding affinity for the ERβ over the ERα.

<span class="mw-page-title-main">5α-Dihydronorethisterone</span> Chemical compound

5α-Dihydronorethisterone is a major active metabolite of norethisterone (norethindrone). Norethisterone is a progestin with additional weak androgenic and estrogenic activity. 5α-DHNET is formed from norethisterone by 5α-reductase in the liver and other tissues.

<span class="mw-page-title-main">Trendione</span> Chemical compound

Trendione, also known as estra-4,9,11-triene-3,17-dione, is an androgen prohormone as well as metabolite of the anabolic steroid trenbolone. Trendione is to trenbolone as androstenedione is to testosterone. The compound is inactive itself, showing more than 100-fold lower affinity for the androgen and progesterone receptors than trenbolone. It is a designer steroid and has been sold on the internet as a "nutritional supplement". Trendione is listed in the United States Designer Anabolic Steroid Control Act of 2014.

References

  1. ↑ Isenmann E, Ambrosio G, Joseph JF, Mazzarino M, de la Torre X, Zimmer P, et al. (July 2019). "Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans". Archives of Toxicology. 93 (7): 1807–1816. doi:10.1007/s00204-019-02490-x. hdl: 11573/1291269 . PMID   31123801. S2CID   163166547.
  2. ↑ Thummel CS, Chory J (December 2002). "Steroid signaling in plants and insects--common themes, different pathways". Genes & Development. 16 (24): 3113–29. doi: 10.1101/gad.1042102 . PMID   12502734.
  3. ↑ Handler AM (September 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. PMID   6813165.
  4. ↑ Cohen PA, Sharfstein J, Kamugisha A, Vanhee C (April 2020). "Analysis of Ingredients of Supplements in the National Institutes of Health Supplement Database Marketed as Containing a Novel Alternative to Anabolic Steroids". JAMA Network Open. 3 (4): e202818. doi:10.1001/jamanetworkopen.2020.2818. PMC   7160690 . PMID   32293681.
  5. ↑ Wilborn CD, Taylor LW, Campbell BI, Kerksick C, Rasmussen CJ, Greenwood M, Kreider RB (December 2006). "Effects of methoxyisoflavone, ecdysterone, and sulfo-polysaccharide supplementation on training adaptations in resistance-trained males". Journal of the International Society of Sports Nutrition. 3 (2): 19–27. doi: 10.1186/1550-2783-3-2-19 . PMC   2129166 . PMID   18500969.
  6. ↑ Simakin SY (1988). "The Combined Use of Ecdisten and the Product'Bodrost'during Training in Cyclical Types of Sport". Scientific Sports Bulletin: 2.
  7. ↑ Gadzhieva RM, Portugalov SN, Paniushkin VV, Kondrat'eva II (1995). "[A comparative study of the anabolic action of ecdysten, leveton and Prime Plus, preparations of plant origin.]". Eksperimental'naia i Klinicheskaia Farmakologiia. 58 (5): 46–8. PMID   8704590.
  8. ↑ Báthori M, Tóth N, Hunyadi A, Márki A, Zádor E (2008). "Phytoecdysteroids and anabolic-androgenic steroids--structure and effects on humans" (PDF). Current Medicinal Chemistry. 15 (1): 75–91. doi:10.2174/092986708783330674. PMID   18220764.
  9. ↑ Smetanin BY (1986). The influence of preparations of plant origin on physical work capacity (Report). The Russian Ministry of Public Health.
  10. ↑ Fadeev BG. Comments on the Results of Retibol in the Practice of Athletic Training and Rehabilitation (Report). Natural Sports Research Institute.
  11. ↑ Azizov AP, Seĭfulla RD, Ankudinova IA, Kondrat'eva II, Borisova IG (1998). "[The effect of the antioxidants elton and leveton on the physical work capacity of athletes]". Eksperimental'naia i Klinicheskaia Farmakologiia (in Russian). 61 (1): 60–2. PMID   9575416.
  12. ↑ Isenmann E, Ambrosio G, Joseph JF, Mazzarino M, de la Torre X, Zimmer P, et al. (July 2019). "Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans". Archives of Toxicology. 93 (7): 1807–1816. doi:10.1007/s00204-019-02490-x. hdl: 11573/1291269 . PMID   31123801. S2CID   163166547.
  13. ↑ Parr MK, Zhao P, Haupt O, Ngueu ST, Hengevoss J, Fritzemeier KH, Piechotta M, Schlörer N, Muhn P, Zheng WY, Xie MY, Diel P (September 2014). "Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone". Molecular Nutrition & Food Research. 58 (9): 1861–72. doi:10.1002/mnfr.201300806. PMID   24974955.
  14. ↑ "Ecdysterone: Definition, Benefits, & Side Effects". Turkesterone.com.
  15. ↑ Saez E, Nelson MC, Eshelman B, Banayo E, Koder A, Cho GJ, Evans RM (December 2000). "Identification of ligands and coligands for the ecdysone-regulated gene switch" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 97 (26): 14512–7. Bibcode:2000PNAS...9714512S. doi: 10.1073/pnas.260499497 . PMC   18950 . PMID   11114195.


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