AGE-DEPENDENT CHANGES IN THE FUNCTION AND MORPHOLOGY OF MITOCHONDRIA OF RAT ADRENAL ZONA-FASCICULATA

The function and morphology of adrenal zona-fasciculata (ZF) mitochond ria were studied in 4-, 10- and 16-month-old rats, since in this speci es ageing causes a marked decline in glucocorticoid secretion coupled with high levels of circulating ACTH. Dispersed intact ZF cells displa yed a significant age-dependent impairment of their basal pregnenolone (PREG) secretion, but isolated ZF mitochondria showed an increased ca pacity to convert cholesterol to PREG (the first rate-limiting step of steroid synthesis). These data are in keeping with the contention tha t the age-related deficit of rat ZF secretion is located prior to the activity of intramitochondrial cholesterol side-chain cleaving enzymes (cytochrome-P450(scc)). Stereology showed a notable age-dependent inc rease in the number of mitochondria per unit cell-volume, coupled with a marked decrease in their average volume. The width of the mitochond rial intermembrane space remained unchanged, but its average volume st rikingly decreased. This last finding fits well with the enhanced capa city of mitochondria to produce PREG, since intermembrane space is an acqueous barrier to the translocation of free cholesterol from the out er membrane to the cristae, where cytochrome-P450(scc) is located. In conclusion, the hypothesis is advanced that all these age-related func tional and morphological mitochondrial changes are an ACTH-dependent c ompensatory response enabling ZF cells to partially counteract their d ecreased glucocorticoid secretory capacity, which in turn is due;to th e impaired utilization of intracytoplasmic stores of cholesterol ester s.