Aljaber, Maneera Y;
Orie, Nelson N;
Raees, Asmaa;
Kraiem, Suhail;
Al-Jaber, Mashael;
Samsam, Waseem;
Hamza, Mostafa M;
... Almaadheed, Mohammed; + view all
(2022)
Downregulation of CYP17A1 by
20-hydroxyecdysone: plasma progesterone
and its vasodilatory properties.
Future Science OA
10.2144/fsoa-2022-0006.
(In press).
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Abstract
Aim: To investigate the effect of 20-hydroxyecdysone on steroidogenic pathway genes and plasma progesterone, and its potential impact on vascular functions. Methods: Chimeric mice with humanized liver were treated with 20-hydroxyecdysone for 3 days, and hepatic steroidogenic pathway genes and plasma progesterone were measured by transcriptomics and GC–MS/MS, respectively. Direct effects on muscle and mesenteric arterioles were assessed by myography. Results: CYP17A1 was downregulated in 20-hydroxyecdysone-treated mice compared with untreated group (p = 0.04), with an insignificant increase in plasma progesterone. Progesterone caused vasorelaxation which was blocked by 60 mM KCl, but unaffected by nitric oxide synthase inhibition. Conclusion: In the short term, 20-hydroxyecdysone mediates CYP17A1 downregulation without a significant increase in plasma progesterone, which has a vasodilatory effect involving inhibition of voltage-dependent calcium channels, and the potential to enhance 20-hydroxyecdysone vasorelaxation.
| Type: | Article |
|---|---|
| Title: | Downregulation of CYP17A1 by 20-hydroxyecdysone: plasma progesterone and its vasodilatory properties |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.2144/fsoa-2022-0006 |
| Publisher version: | https://doi.org/10.2144/fsoa-2022-0006 |
| Language: | English |
| Additional information: | This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | 20-hydroxyecdysone • CYP17A1 • ecdysteroid • hepatic transcriptome • humanized liver • mesenteric arteriole • muscle arteriole • progesterone • vasodilation • voltage-dependent calcium entry |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10152365 |
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