Ecdysteroids: A novel class of anabolic agents?

Parr, Maria Kristina; Botrè, Francesco; Naß, Alexandra; Hengevoß, Jonas; Diel, Patrick; Wolber, Gerhard

doi:10.5604/20831862.1144420

Cited by 76 publications

(84 citation statements)

References 18 publications

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“…by phosphorylation (21). Some evidence for a direct binding was provided by in silico modelling (22), but this certainely does not represent a definite proof, as the result may strongly depend on the model used, and an opposite conclusion was drawn by Lapenna et al (23).…”

Section: How Do Ecdysteroids Work?mentioning

confidence: 92%

20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor

Lafont

Raynal

Serova

et al. 2020

Preprint

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20-Hydroxyecdysone (20E) is a steroid hormone that plays a key role in insect development through nuclear ecdysone receptors (EcRs) and at least one membrane GPCR receptor (DopEcR) and displays numerous pharmacological effects in mammals. However, its mechanism of action is still debated, involving either an unidentified GPCR or the estrogen ERβ receptor. The goal of our study was to better understand 20E mechanism of action.A mouse myoblast cell line (C2C12) and the gene expression of myostatin (a negative regulator of muscle growth) was used as a reporter system of anabolic activity. Experiments using protein-bound 20E established the involvement of a membrane receptor. 20E-like effects were also observed with Angiotensin- (1-7), the endogenous ligand of Mas. Additionally, the effect on myostatin gene expression was abolished by Mas receptor knock-down using small interfering RNA (siRNA) or pharmacological inhibitors.17-Estradiol (E2) also inhibited myostatin gene expression, but proteinbound E2 was inactive, and E2 activity was not abolished by angiotensin-(1-7) antagonists. A mechanism involving cooperation between Mas receptor and a membrane-bound palmitoylated estrogen receptor is proposed.The possibility to activate the Mas receptor with a safe steroid molecule is consistent with the pleiotropic pharmacological effects of ecdysteroids in mammals and indeed this mechanism may explain the close similarity between angiotensin-(1-7) and 20E effects. Our findings open a lot of possible therapeutic developments by stimulating the protective arm of the renin-angiotensin-aldosterone system (RAAS) with 20E.

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Section: How Do Ecdysteroids Work?mentioning

confidence: 92%

20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor

Lafont

Raynal

Serova

et al. 2020

Preprint

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“…The mechanism of action includes binding and activation of estrogen receptor (ER) signaling. Selective ER antagonists block ecdysterone stimulated myotubular growth in vitro, and in silico molecular docking experiments support an ERβ-mediated mode of ecdysterone action (Parr et al 2014(Parr et al , 2015. Conversely, in silico studies imply estrogenic activation of EcR in arthropods (Swetha et al 2016).…”

Section: Ecdysteroid Anabolicsmentioning

confidence: 92%

“…Conversely, in silico studies imply estrogenic activation of EcR in arthropods (Swetha et al 2016). The anabolic potential of ecdysterone as a dietary supplement in humans is such that it could yet be prohibited as a performance-enhancing drug by the World Anti-Doping Agency (Parr et al 2015).…”

Section: Ecdysteroid Anabolicsmentioning

confidence: 99%

On gonads and gadflies: the estrus angle

Hillier

2017

Journal of Endocrinology

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The first sex steroid to be crystallized was the vertebrate ovarian hormone, estrone -a less potent metabolite of 17β-estradiol, which in mammals stimulates the female urge to mate (estrus). The gadfly (Greek oistros) lent its name to the process of estrus, as an insect that bites and torments in classical Greek mythology. With the purification and crystallization of a moult-inducing steroid (ecdysone) from insects, an interesting parallel emerged between mating and moulting in lower mammals and arthropods. Ecdysterone (potent ecdysone metabolite) has anabolic effects in mammalian muscle cells that can be blocked by selective estrogen receptor antagonists. Insects utilize ecdysteroids in similar ways that vertebrates use estrogens, including stimulation of oocyte growth and maturation. Ecdysteroids also modify precopulatory insect mating behaviour, further reinforcing the gonad-gadfly/mate-moult analogy.

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“…The most well-known effect of ecdysone is probably its hypertrophic and anabolic effect that increases protein synthesis in diverse organ systems in rodents and humans, including liver, kidney and most strikingly in muscles [8]. Ecdysone has been verified to be one of the major active ingredients in numerous dietary supplements that are marketed as "natural anabolic agents" and are used by sportsmen or bodybuilders [43]. However, kidney hypertrophy is known to be a prelude to progressive chronic kidney injury.…”

Section: Discussionmentioning

confidence: 99%

Ecdysone Elicits Chronic Renal Impairment via Mineralocorticoid-Like Pathogenic Activities

Wang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ecdysteroids are steroidal insect molting hormones that also exist in herbs. Ecdysteroid-containing adaptogens have been popularly used to improve well-being and by bodybuilders for muscle growth. However, the use of ecdysone in mammals is also associated with kidney growth and enlargement, indications of disturbed kidney homeostasis. The underlying pathogenic mechanism remains to be clarified. Methods: Virtual screening tools were employed to identify compounds that are homologous to ecdysone and to predict putative ecdysone-interacting proteins. The kidney effect of ecdysone was examined in vitro and in vivo and compared with that of aldosterone. Cellular apoptosis was estimated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Cell motility was assessed by scratch-wound cell migration assay. Blood urea nitrogen was measured to evaluate renal function. Western immunblot analysis was employed to determine the expression profile of interested proteins. Results: Computational molecular structure analysis revealed that ecdysone is highly homologous to aldosterone. Moreover, virtual screening based on compound-protein interaction profiles identified the Mineralocorticoid Receptor (MR) to potentially interact with ecdysone. Accordingly, to assess potential biological functions of ecdysone in mammals, ecdysone was applied to mineralocorticoid-sensitive inner medullar collecting duct cells. Ecdysone induced mesenchymal accumulation of extracellular matrix and epithelial dedifferentiation characterized by de novo expression of α-smooth muscle actin. In addition, ecdysone elicited cellular apoptosis and retarded cell motility, akin to the effect of aldosterone. In vivo, daily treatment of mice with ecdysone increased cell apoptosis in the kidney, impaired renal function and elicited early signs of renal fibrogenesis, marked by deposition of collagen and fibronectin in tubulointerstitium, reminiscent of the action of aldosterone. The MR signaling pathway is likely responsible for the cellular and pathobiological effects of ecdysone, as evidenced by strong ecdysone-induced MR nuclear translocation in renal tubular cells both in vitro and in vivo, while blockade of MR by concomitant spironolactone treatment largely abolished the detrimental effects of ecdysone. Conclusion: Our findings suggest that ecdysone induces mineralocorticoid-dependent activities that impair renal function and elicit renal injury.

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Ecdysteroids: A novel class of anabolic agents?

Cited by 76 publications

References 18 publications

20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor

20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor

On gonads and gadflies: the estrus angle

Ecdysone Elicits Chronic Renal Impairment via Mineralocorticoid-Like Pathogenic Activities

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