The Sound of Evolution
Metyrapone
美替拉酮
Mechanism of action:
Metyrapone 是一種腎上腺皮質類固醇合成抑制劑（adrenal steroidogenesis inhibitor），屬於吡啶類（pyridine）衍生物。Metyrapone 會抑制位於腎上腺皮質束狀帶（zona fasciculata）的 11β-羥化酶（11β-hydroxylase，CYP11B1）。該酵素負責將 11-脫氧皮質醇（11-deoxycortisol）轉變成皮質醇（cortisol），以及 11-脫氧皮質酮轉化（11-deoxycorticosterone）為皮質酮（corticosterone）。當 11β-羥化酶被 metyrapone 抑制後，皮質醇與皮質酮的生成下降，會導致對下視丘-腦下垂體的負回饋減少，使促腎上腺皮質素（adrenocorticotropic hormone）的生成量會上升。
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.