Adrenalectomy decreases the sphingomyelin and cholesterol content of fat cell ghosts.

Adrenalectomy produces a significant fall in the sphingomyelin and cholesterol content of ghosts isolated from rat epididymal fat cells. Previous studies from this laboratory have demonstrated an effect of dexamethasone in vitro to increase the sphingomyelin content of fat cell ghosts obtained from adrenalectomized animals. The present study demonstrates that adrenalectomy influences the membrane lipid content. Dexamethasone, in vitro, was found to increase the sphingomyelin of epididymal fat cell ghosts isolated from intact animals, as it previously had been shown to affect epididymal fat cell ghosts obtained from adrenalectomized animals. Incubation with dexamethasone for 3 h had no effect on the cholesterol content of the ghosts. Adrenalectomy, on the other hand, resulted in a significant decrease in the cholesterol content of the fat cell ghosts.

Corticosteroid-induced lipid changes in rat liver microsomes.

An influence of corticosteroids on the phospholipid composition of several tissues has been demonstrated previously. Increases in the activity of rat liver microsomal cytochrome c reductase and aryl hydrocarbon hydroxylase after corticoid administration were also demonstrated. The phospholipid composition of liver microsomes is now reported to be altered by similar corticosteroid treatment. Phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin levels in rat liver microsomes were decreased significantly after in vivo cortisol administration. The levels of palmitic, stearic, oleic, linoleic, and arachidonic acids in phosphatidylcholine and of palmitic acid in phosphatidylserine-phosphatidylinositol were also affected. Cholesterol was increased after adrenalectomy and decreased to control levels after the administration of cortisol. Some of the microsomal enzymes which are affected by corticosteroids or adrenalectomy are known to require phospholipids for full activity. The alteration of enzyme activities and membrane phospholipid composition by similar dosage schedules of corticosteroids suggests a possible relation between the two effects. By affecting the lipid composition of the membranes, corticosteroids may regulate or modulate the activity of the lipid-requiring enzyme systems.

Dexamethasone effect on the phospholipid content of isolated fat cell ghosts from adrenalectomized rats.

The lipid composition of sonicated ghosts from isolated fat cells has been investigated. Epididymal fat cells from adrenalectomized rats were incubated with and without 8 x 10(-8) M dexamethasone for 3 h. Phospholipids and cholesterol were isolated from membrane ghosts prepared from these cells. There was a 61% increase in membrane sphingomyelin from cells incubated with dexamethasone (P less than 0.025). No significant change was observed in other phospholipids, cholesterol, or fatty acid components of the phospholipids.

An effect of corticosteroids and 100% oxygen on aryl hydrocarbon hydroxylase, cytochrome-c reductase, and free radical formation by rat lung microsomes.

Activity of aryl hydrocarbon hydroxylase (AHH), cytochrome c-reductase, and NADPH oxidase, and epinephrine oxidation to adrenochrome were determined in lung microsomes from intact, adrenalectomized, and adrenalectomized cortisol-treated female rats under ambient and hyperoxic conditions. Microsomal adrenochrome formation, which is initiated by superoxide anion or other free radicals, was increased by adrenalectomy and decreased by cortisol treatment. Exposure of animals to 100% oxygen caused a further increase in adrenochrome formation. NADPH-cytochrome c-reductase and AHH activities were increased in incubations of microsomes from animals which had received cortisol in vivo while adrenalectomy led to decreases activity. NADPH oxidase activity was increased by cortisol in lung microsomes in the presence of either epinephrine or cytochrome c. Epinephrine conversion to adrenochrome in the presence of lung microsomes was blocked by SOD, but NADPH-cytrochrome c-reductase and AHH activity were unaffected.

Inhibition of leukocyte superoxide anion production by cortisol administration to normal subjects.

Superoxide anion production was suppressed in leukocytes obtained at two or four hours following oral administration of 50 to 100 mg of cortisol to normal subjects. The suppression lasted at least 4 hours but was not present at 24 hours. The measurement of superoxide anion production by leukocytes appears to be a convenient method for the serial estimation of an important biologic effect of corticosteroids in human subjects.

Plasma ACTH levels in stressed and nonstressed adrenalectomized rats.

Following adrenalectomy there is a triphasic response of ACTH secretion characterized by an initial high rise immediately following the adrenalectomy, secondary to the stress of the procedure. This is followed by a fall to resting ACTH secretion until a steady state is reached 1 to 2 weeks following adrenalectomy at levels about 10 times normal. The ability to respond to stress with increased ACTH secretion is not lost at any time following adrenalectomy.

Corticosteroids increase superoxide anion production by rat liver microsomes.

Superoxide anion production by liver microsomes from intact, adrenalectomized, and cortisoltreated adrenalectomized rats has been determined. The amount formed was roughly proportionate to the amount of cortisol given, and a similar response was seen in the activity of NADPH-cytochrome c reductase. The amount of measurable superoxide anion was markedly reduced by the addition of superoxide dismutase. The increased production of this potent free radical with cortisol therapy suggests that its formation may contribute to some of the harmful effects of corticosteroids given in more than physiologic amounts.