Markowska A, Rebuffat P, Gottardo G, Mazzochi G, Nussdorfer G G
Department of Histology and Embryology, School of Medicine, Poznan, Poland.
Histol Histopathol. 1994 Apr;9(2):263-8.
The function and morphology of adrenal zona-fasciculata (ZF) mitochondria were studied in 4-, 10- and 16-month-old rats, since in this species ageing causes a marked decline in glucocorticoid secretion coupled with high levels of circulating ACTH. Dispersed intact ZF cells displayed a significant age-dependent impairment of their basal pregnenolone (PREG) secretion, but isolated ZF mitochondria showed an increased capacity to convert cholesterol to PREG (the first rate-limiting step of steroid synthesis). These data are in keeping with the contention that the age-related deficit of rat ZF secretion is located prior to the activity of intramitochondrial cholesterol side-chain cleaving enzymes (cytochrome-P450scc). Stereology showed a notable age-dependent increase in the number of mitochondria per unit cell-volume, coupled with a marked decrease in their average volume. The width of the mitochondrial intermembrane space remained unchanged, but its average volume strikingly decreased. This last finding fits well with the enhanced capacity of mitochondria to produce PREG, since intermembrane space is an aqueous barrier to the translocation of free cholesterol from the outer membrane to the cristae, where cytochrome-P450scc is located. In conclusion, the hypothesis is advanced that all these age-related functional and morphological mitochondrial changes are an ACTH-dependent compensatory response enabling ZF cells to partially counteract their decreased glucocorticoid secretory capacity, which in turn is due to the impaired utilization of intracytoplasmic stores of cholesterol esters.
对4月龄、10月龄和16月龄大鼠的肾上腺束状带（ZF）线粒体的功能和形态进行了研究，因为在该物种中，衰老会导致糖皮质激素分泌显著下降，同时循环促肾上腺皮质激素（ACTH）水平升高。分散的完整ZF细胞显示出其基础孕烯醇酮（PREG）分泌存在明显的年龄依赖性损伤，但分离的ZF线粒体将胆固醇转化为PREG（类固醇合成的第一步限速步骤）的能力增强。这些数据与以下观点一致，即大鼠ZF分泌的年龄相关缺陷位于线粒体内胆固醇侧链裂解酶（细胞色素P450scc）活性之前。体视学显示，单位细胞体积中线粒体数量有显著的年龄依赖性增加，同时其平均体积显著减小。线粒体膜间隙的宽度保持不变，但其平均体积显著减小。这一最新发现与线粒体产生PREG的能力增强非常吻合，因为膜间隙是游离胆固醇从外膜转运到细胞色素P450scc所在的嵴的水性屏障。总之，提出了以下假说：所有这些与年龄相关的线粒体功能和形态变化都是一种ACTH依赖性的代偿反应，使ZF细胞能够部分抵消其糖皮质激素分泌能力的下降，而糖皮质激素分泌能力下降又是由于细胞质内胆固醇酯储存利用受损所致。
