Downregulation of CYP17A1 by 20-hydroxyecdysone: plasma progesterone and its vasodilatory properties

Autor: Maneera Y Aljaber, Nelson N Orie, Asmaa Raees, Suhail Kraiem, Mashael Al-Jaber, Waseem Samsam, Mostafa M Hamza, David Abraham, Norman M Kneteman, Alka Beotra, Vidya Mohamed-Ali, Mohammed Almaadheed
Rok vydání: 2022
Předmět:
Zdroj: Future Science OA. 8
ISSN: 2056-5623
DOI: 10.2144/fsoa-2022-0006
Popis: 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.
Databáze: OpenAIRE