Publication: Age-dependent changes in the function and morphology of mitochondria of rat adrenal zona fasciculata
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Date
1994
Authors
Markowska, A. ; Rebuffat, P. ; Gottardo, Giuseppe ; Mazzocchi, G. ; Nussdorfer, G.G.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
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 acqueous 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.
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