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

Authors :: Aljaber MY
Orie NN
Raees A
Kraiem S
Al-Jaber M
Samsam W
Hamza MM
Abraham D
Kneteman NM
Beotra A
Mohamed-Ali V
Almaadheed M
Source :: Future science OA [Future Sci OA] 2022 Jul 07; Vol. 8 (6), pp. FSO805. Date of Electronic Publication: 2022 Jul 07 (Print Publication: 2022).
Publication Year :: 2022
Abstract: Aim: To investigate the effect of 20-hydroxyecdysone on steroidogenic pathway genes and plasma progesterone, and its potential impact on vascular functions.<br />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.<br />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.<br />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.<br /> (© 2022 The Authors.)

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