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

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 KCI, 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. Plain language summary: The study looked at how the level of the hormone progesterone might be changed by taking a steroid called 20-hydroxyecdysone, which can be found in dietary supplements, and how this might affect the arteries that carry blood to the muscles. The substance was given to mice for 3 days before samples of blood and liver were taken and measured. The progesterone level did not increase appreciably during this short period, but the gene (CYP17A1) which produces the enzyme that breaks it down was reduced substantially. This was both able to cause the arteries to expand and to help 20-hydroxyecdysone expand them.