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At least 1,189 records · Page 66Linked to original sources
PubMed1992

[Suppression of the adrenal cortex by enoximone. A proband study with documentation of the hemodynamic course].

In contrast to the bipyridine derivatives amrinone and milrinone, the phosphodiesterase III/IV inhibitor enoximone is an imidazolone that creates the possibility of inhibiting adrenal steroid synthesis, as has already been demonstrated for other imidazoles, e.g. ketoconazole and etomidate. To clarify this point we carried out a double-blind sequential study in seven healthy volunteers. METHODS. After obtaining the approval of the ethics committee and the written consent of the volunteers, 1.25 mg/kg enoximone or saline was infused intravenously over a period of 20 min using a randomized crossover design with an interval of at least 5 days between the two trials. Twenty minutes after administration of the drug, 250 micrograms ACTH was injected. Plasma cortisol was measured prior to stimulation of the adrenal cortex and 30, 60 and 120 min afterwards; levels of aldosterone and 11-desoxy-cortisol were determined after 60 min. Standard radioimmunoassays were used. Haemodynamic parameters were measured non-invasively. RESULTS. In contrast to the placebo, enoximone resulted in a significant (P < 0.01) increase in the cardiac index (from 3.2 +/- 0.7 to 3.9 +/- 0.9 l min-1 m-2) and heart rate (from 69 +/- 11 to 81 +/- 8 min-1) and a decrease in peripheral resistance (from 1120 +/- 202 to 894 +/- 183 dyn s cm-5); blood pressure fell only slightly. Following injection of ACTH there were significant increases in cortisol (from 63 +/- 29 to 274 +/- 58 micrograms/l), aldosterone (from 86 +/- 37 to 300 +/- 105 ng/l) (both P < 0.001) and 11-desoxycortisol (from 5.3 +/- 1.2 to 9.8 +/- 4.6 micrograms/l; P < 0.05). There was no difference between enoximone and placebo at any time (P > 0.2). CONCLUSIONS. This study confirms the inodilation caused by enoximone. The normal response to ACTH rules out a direct inhibitory effect of a loading dose of 1.25 mg enoximone on the adrenal cortex. As the concentration of the major metabolite of enoximone, the sulphoxide, has been shown to surmount that of the parent drug after 40 min, this also holds true for the metabolite. We conclude that in contrast to etomidate, which causes a substantial reversible adrenal suppression after a single dose of 0.2 mg/kg, enoximone 1.25 mg/kg did not interfere with corticosteroid synthesis or release. Taking into account the metabolism and pharmacokinetics of this inodilator, there is no reason to expect an inhibitory effect even after repeated dosage.

Adrenal Cortex↗
PubMedDate not supplied

[The patterns in the functioning of the hypothalamo-hypophyseal-adrenal cortex system].

Main principles of functioning of the hypothalamus-hypophysis-adrenal cortex system (HHACS) in conditions of stress activation and rhythmic excitation and inhibition are characterized. Interrelations between input signals, disturbing the HHACS, and output parameters of its activity, are described. The role of central and peripheral parts of HHACS in the realization of the principles of its functioning is analyzed. The concept on the significance of HHACS construction as a system of three hormonal links is considered. The dependence of adaptive capacities of the body on the HHACS state is characterized. Recently discovered features of corticosteroid hormones as agents increasing adaptive resources--the antinociceptive and the antiulcer actions--are discussed.

Adaptation, Physiological↗
PubMed1976

Purification and characterization of adrenal cortex mitochondrial cytochrome P-450 specific for cholesterol side chain cleavage activity.

Cytochrome P-450 was purified from bovine adrenal cortex mitochondria by affinity chromatography using an octylamine-substituted Sepharose column. The resulting optically clear preparation was stable at -20 degrees for months. The specific concentration of cytochrome P-450 in the preparation was about 5 nmol of heme per mg of protein. The preparations were free of adrenodoxin, adrenodoxin reductase, phospholipids, and other heme contaminations. Polyacrylamide gel electrophoresis of the purified cytochrome P-450 preparation treated with sodium dodecyl sulfate and mercaptoethanol showed a single major band with a molecular weight of about 60,000. The optical absorption spectra of the preparation exhibited Soret maxima at 416, 416, and 448 nm for the Fe3+, Fe2+ and the C.Fe2+ complex, respectively. The EPR spectrum showed the characteristic features of the low spin form of ferric cytochrome P-450 with principal components 1.914, 2.241, and 2.415 of the g-tensor. The circular dichroism spectrum revealed two large negative ellipticities at 412 and 350 nm. Fluorescence spectra showed an excitation maximum at 285 nm and an emission maximum at 305 nm with a shoulder at 330 nm as the cytochrome P-450 molecule is excited at 285 nm, or an emission maximum at 335 nm when the cytochrome molecule is excited at 305 nm. After reconstitution with adrenodoxin and its reductase, this cytochrome P-450 was highly active for cholesterol desmolase with an NADPH-generating system as electron donor but was not active for steroid 11beta-hydroxylase.

Adrenal Cortex↗
PubMed1997

Ultrastructure of the adrenal cortex of hibernating, arousing, and euthermic dormouse, Muscardinus avellanarius.

BACKGROUND: The adrenal gland is a key organ for hibernation (a condition characterized by striking reduction of body functions). Very limited information is available on the fine structure of the gland during hibernation and on the periodical arousal from hibernation. METHODS: Dormice (Muscardinus avellanarius) were maintained in an external animal house and allowed to hibernate spontaneously (November). Arousal was induced in March by exposure to daylight. Euthermic, active dormice were captured in June. The adrenals were taken from four hibernating, three arousing, and four euthermic dormice and processed for resin embedding. The ultrastructure of the adrenal cortex was investigated by transmission electron microscopy. RESULTS: In the zona glomerulosa of hibernating and arousing dormice, the smooth endoplasmic reticulum was prominent in comparison with euthermic animals, and mitochondria showed abundant vesicular cristae. The zona fasciculata and zona reticularis did not show consistent differences, apart from a lower cell lipid content in the outer portion of zona fasciculata of arousing dormice. CONCLUSIONS: The zona glomerulosa showed signs of increased activity during hibernation. This finding is supported by previous biochemical data demonstrating increased production of renin and aldosterone during such extreme physiological conditions. Activation of the zona glomerulosa in hibernation is probably adaptive to a condition of drastically reduced salt intake.

Adrenal Cortex↗
PubMed2004

Aging of the human adrenal cortex.

The most striking age-related change in the human adrenal cortex is the decline in secretion of dehydroepiandrosterone and its sulfate, steroids synthesized by the inner zone of the cortex, the zona reticularis. Because these steroids are of essentially unknown function, the importance of this age-related change is the subject of considerable debate. It is likely that the age-related change in these steroids results from loss of zona reticularis cells or impairment of their function. During aging, cumulative damage to the zona reticularis could occur through ischemia-related infarcts and other causes of cell death. Cellular senescence could contribute to a loss of the ability of the tissue to replace lost cells. In contrast, feedback mechanisms that regulate adrenocortical growth cause compensatory local tissue hyperplasias called nodules. The effect of imperfect repair of damage combined with compensatory overgrowth in the form of nodules leads to an increasingly abnormal tissue architecture.

Adrenal Cortex↗
PubMed1980

[Surgical treatment of the Itsenko-Cushing syndrome accompanying an adrenal cortex neoplasm].

The data of remote observations of 39 operated patients with adrenal cortex tumors were analyzed as well as the functional state of the hypothalamo-hypophysial system and morphological investigations of the adrenals removed. In the light of the results obtained the questions of surgical methods and choice of the operation volume are discussed which can liberate the patients of the Itsenko-Cushing syndrome.

Adenoma↗
PubMed1977

[Diurnal rhythm of the adrenal cortex function in patients with circulatory disorders].

The blood hydrocortisone and corticosterone content and the aldosterone level in the urine were determined for 24 hours in patients with congenital heart disease before and after operative treatment. In patients with symptoms of cardiac insufficiency both glucocorticoid and mineralocorticoid activity of the adrenal cortex was marked by deviations from the diurnal physiological rhythm. This is reflected in the continuous activation of the adrenal cortex during 24 hours; activation of mineralocorticoid function in the evening and during the night is a particularly characteristic phenomenon.

Adolescent↗
PubMed2000

Leptin prolonged administration inhibits the growth and glucocorticoid secretion of rat adrenal cortex.

Leptin is an adipose-tissue secreted hormone, that acts to decrease caloric intake and to increase energy expenditure. Some of the leptin effects on the energy balance are known to be mediated by the hypothalamo-pituitary-adrenal (HPA) axis, but the role of this cytokine in the regulation of the growth and steroidogenic capacity of adrenal cortex is still controversial. Therefore, the present study was designed to explore the long-term effects of native leptin[1-147] and its biologically active fragment leptin[116-130] (6 daily subcutaneous injection of 20 nmol/kg) on the rat HPA axis. Leptin[1-147] and leptin[116-130] caused a significant adrenal atrophy, which was mainly due to the decrease in the volume of zona fasciculata (ZF) and in the number of its parenchymal cells. Both leptins provoked a marked drop in the plasma concentrations of ACTH and corticosterone, the main hormone produced by ZF cells. The effects of leptin[116-130] were more intense than those of leptin[1-147]. Leptin[1-147], but not its fragment, evoked a clear-cut rise in the plasma concentration of aldosterone. Collectively, these findings indicate that prolonged leptin administration, by inhibiting pituitary ACTH release, exerts a potent suppressive action on the growth and glucocorticoid secretory capacity of the adrenal cortex in the rat. The mechanism(s) underlying the aldosterone secretagogue action of native leptin remain(s) to be investigated.

Adrenal Cortex↗
PubMed1982

Cytochrome P-45011 beta and P-450scc in adrenal cortex: zonal distribution and intramitochondrial localization by the horseradish peroxidase-labeled antibody method.

In an attempt to elucidate the regulation mechanism(s) of adrenocortical steroidogenesis, cytochrome P-450scc and cytochrome P-45011 beta were localized in bovine adrenal glands by the direct peroxidase-labeled antibody method. At the light microscopic level, parenchymal cells of the zona fasciculata and the zona reticularis stained heavily for both cytochromes, while the parenchymal cells of zona glomerulosa stained lightly for both. At the electron microscopic level, these two cytochromes were associated with the matrix side of the inner mitochondrial membranes of parenchymal cells from all three zones of the adrenal cortex. The association of cytochrome P-450 with the inner mitochondrial membrane, in a manner similar to that previously reported for adrenodoxin and adrenodoxin reductase (F Mitani, Y Ishimura, S Izumi, K Watanabe, Acta Endocrinol 90:317, 1979), establishes that the steroid monooxygenase systems exist at this site. The degree of immunocytochemical staining within a single cell varied from one mitochondrion to another: some stained intensely along the entire inner membrane, including the cristae, some stained only along segments of the inner membrane, and some did not stain at all. This heterogeneity in staining was observed in mitochondria stained in situ as well as in isolated mitochondria. These findings suggest that there is a heterogeneity in steroidogenesis among mitochondria contained within a single cell of the adrenal cortex.

Adrenal Cortex↗