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

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

doi:10.2144/fsoa-2022-0006

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

Future Sci OA. 2022 Jul 7;8(6):FSO805. doi: 10.2144/fsoa-2022-0006. eCollection 2022 Jul.

Authors

Maneera Y Aljaber¹, Nelson N Orie^{1

2}, Asmaa Raees¹, Suhail Kraiem¹, Mashael Al-Jaber¹, Waseem Samsam¹, Mostafa M Hamza³, David Abraham², Norman M Kneteman^{4

5}, Alka Beotra¹, Vidya Mohamed-Ali^{1

2}, Mohammed Almaadheed^{1

2}

Affiliations

¹ Anti-Doping Laboratory Qatar, Sports City Road, Doha, 27775, Qatar.
² Centre of Metabolism & Inflammation, Division of Medicine, Royal Free Campus, University College London, Rowland Hill Street, London, NW3 2PF, UK.
³ Qatar Computing Research Institute, Hamad bin Khalifa University, Doha, 5825, Qatar.
⁴ KMT Hepatech Inc., PhoenixBio Group, 11421 Saskatchewan Drive, Edmonton, AB, T6G 2M9, Canada.
⁵ Division of Transplantation Surgery, University of Alberta, Edmonton, Canada.

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.

Keywords: 20-hydroxyecdysone; CYP17A1; ecdysteroid; hepatic transcriptome; humanized liver; mesenteric arteriole; muscle arteriole; progesterone; vasodilation; voltage-dependent calcium entry.