The Sound of Evolution
Metyrapone
Mechanism of action:
Metyrapone is an adrenal steroidogenesis inhibitor and belongs to the pyridine derivatives. Metyrapone inhibits 11β-hydroxylase (CYP11B1), which is located in the zona fasciculata of the adrenal cortex. This enzyme is responsible for converting 11-deoxycortisol into cortisol and 11-deoxycorticosterone into corticosterone. When 11β-hydroxylase is inhibited by metyrapone, cortisol and corticosterone production decreases, reducing negative feedback on the hypothalamus and pituitary gland, which in turn increases adrenocorticotropic hormone production.
Reference(s):
1. Young EA et al. (2007). Sex differences in ACTH pulsatility following metyrapone blockade in patients with major depression. Psychoneuroendocrinology.
2. Johansson MK et al. (2002). Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicol In Vitro.
3. Hermansson V et al. (2007). Comparative CYP-dependent binding of the adrenocortical toxicants 3-methylsulfonyl-DDE and o,p'-DDD in Y-1 adrenal cells. Arch Toxicol.