Mitochondrial 11 β hydroxylation and adrenal morphology in rats bearing a mammotropic, ACTH-secreting pituitary tumor

Abstract

The function and structure of adrenal mitochondria has been studied in rats bearing an ACTH, growth hormone and prolactin secreting tumor (MtT-F4). Basal levels of 11 β hydroxylation of deoxycorticosterone (DOC) in incubated mitochondria were higher in MtT-F4 than in controls ( P < 0.001). The addition of NADH and calcium to controls increased the conversion of DOC to corticosterone ( P < 0.001) but no change was observed in MtT-F4. With addition of NADPH plus calcium, the increase in controls was of a much higher magnitude than that produced in MtT-F4 ( P < 0.05). Calcium alone diminished the high levels of hydroxylation in MtT-F4. Measurement of mitochondrial swelling showed that in the presence of albumin and at 37°C swelling rates in MtT-F4 and controls were similar; however, large amplitude swelling developed in MtT-F4 when albumin was omitted and temperature was lowered to 25°C. ATPase activity was not different in mitochondria from both groups of rats either in the presence or absence of magnesium. The depressive effect of calcium, an uncoupler of oxidative phosphorylation, showed that some form of energy was needed for the high rate of basal hydroxylation in MtT-F4. The diminished response to the nucleotides indicated that probably both the P 450 hydroxylation chain and the transhydrogenase enzyme are impaired in MtT-F4. Electron microscopy of whole adrenal cortex showed a general appearance of hyperfunction. Mitochondria of zona glomerulosa contained inclusions of high electron density, and the outer membrane showed a multillaminar appearance. In zona fasciculata mitochondria showed normal structure, but different electronic density and individual variation in the number of cristae. In contrast, mitochondria of zona reticularis showed normal morphology.