Hornsby P J
Endocr Res. 1986;12(4):469-94. doi: 10.3109/07435808609035451.
The adrenal cortex is the site of the synthesis of the steroid hormones such as the glucocorticoid cortisol and the mineralocorticoid aldosterone. The pathway of biosynthesis of these steroids from cholesterol involves a sequence of transformations using cytochrome P-450 enzymes. The hypothesis presented here is that damage to cytochrome P-450 enzymes on interaction with certain steroids, synthesized by the adrenal cortex itself, may be of pathological and perhaps physiological importance. The interaction between cytochrome P-450 enzymes and these steroids, which act as pseudosubstrates, may form part of the pathogenesis of some steroidogenic enzyme deficiencies, with consequent overproduction of precursor steroids, leading to mineralocorticoid or androgen excess. This interaction is dependent on achieving high concentrations of the pseudosubstrate steroids in the adrenal cortex, which probably occurs as a result of the arrangement of the vasculature in the adrenal gland. High concentrations of steroids may be expected to accumulate in steroidogenic cells, both in culture and in vivo, and may have autoregulating effects. The high content of antioxidant compounds in the adrenal cortex, principally ascorbate, may serve to protect cytochrome P-450 enzymes from the damaging effects of oxygen radical species formed as a result of cytochrome P-450/pseudosubstrate interactions.
肾上腺皮质是合成类固醇激素的场所，如糖皮质激素皮质醇和盐皮质激素醛固酮。这些类固醇由胆固醇生物合成的途径涉及一系列使用细胞色素P-450酶的转化过程。本文提出的假说认为，肾上腺皮质自身合成的某些类固醇与细胞色素P-450酶相互作用时对该酶造成的损伤可能具有病理学意义，甚至可能具有生理学意义。细胞色素P-450酶与这些充当假底物的类固醇之间的相互作用，可能是某些类固醇生成酶缺乏症发病机制的一部分，从而导致前体类固醇的过度产生，进而导致盐皮质激素或雄激素过多。这种相互作用取决于在肾上腺皮质中达到高浓度的假底物类固醇，这可能是由于肾上腺中血管系统的排列所致。无论是在培养中还是在体内，类固醇生成细胞中都可能会积累高浓度的类固醇，并且可能具有自动调节作用。肾上腺皮质中抗氧化化合物的高含量，主要是抗坏血酸盐，可能有助于保护细胞色素P-450酶免受因细胞色素P-450/假底物相互作用而形成的氧自由基的破坏作用。
