[Study of the inhibitory effect of anti-inflammatory corticosteroids on pituitary-adrenal cortex function].
Explore the source record for details and available documents.
SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Studies on the effect of pinealectomy (PX) and melatonin on adrenal cortex of ovariectomized and estradiol replaced rats were performed. Neither PX nor melatonin replacement changed corticosterone output by adrenal homogenate, 11 beta-hydroxylase activity, liver corticosterone metabolism or serum corticosterone level, however, melatonin increased adrenal 5 alpha-reductase activity. On the other hand, PX of 14 months duration resulted in an increase in intraadrenal 5 alpha-reductase activity. PX did not modify estradiol effect on rat adrenal cortex, while concomitant estradiol-melatonin administration increased corticosterone output by adrenal homogenate. Stimulatory effect of estradiol on liver corticosterone metabolism was observed only in the presence of pineal gland or exogenous melatonin. In non of experiments, 45 nmole/ml of melatonin added into incubation medium stimulated adrenal 5 alpha-reductase activity. Obtained results cast doubt on a physiological role of melatonin in regulation of adrenocortical secretory activity in ovariectomized rats and suggest that estradiol effect on the adrenal cortex is not mediated by the pineal gland.
The primary endocrine organs responsible for steroid hormone biosynthesis--the adrenal cortex and gonads--are derived from the urogenital ridge. Several recent discoveries in human and mouse genetics have begun to unravel the complex genetic cascade that dictates adrenocortical cell lineage, proliferation and differentiation. The factors that regulate adrenocortical organogenesis and the maintenance of growth promote or block a cascade of transcription factors that differentially coordinate the proliferation and differentiation of the gland. Here, we outline the developmental milestones of the adrenal cortex with recent contributions to the field, focusing on factors that have been shown to play a role in vivo in humans and mice.
Feminizing tumors of the adrenal cortex in man are very rare. The case is reported of a 66-year-old man who had a carcinoma of the right adrenal cortex which produced various steroid fractions. In the primary tumor and in the second reccurrence the estrogens were dominant. In electron microscopy the tumor cells are poorly differentiated. They may be attributed to the fasciculo-reticular layer and show no signs specific for their secretory activity. The patient died 2 1/2 years after onset of the disease. The case is discussed in the light of the pertinent literature.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Continuous sucrose density gradient subfractions from bovine adrenal medullary microsomes were found to accumulate 45-Ca-2+ in the presence of ATP and ammonium oxalate mainly in subfractions of intermediate density. (Na-++K-+)-ATPase (plasma membrane marker) and Ca-2+-ATPase activities were also concentrated in these intermediate subfractions but thiamine pyrophosphatase (Golgi apparatus marker) was not. NADH oxidase (endoplasmic reticulum marker) activity was distributed throughout all subfractions. 45-Ca-2+ accumulation in adrenal cortical microsomes was found to rise and fall in parallel with thiamine pyrophosphatase but not with (Na-++K-+)-ATPase or NADH oxidase activities. Accumulation of 45-Ca-2+ in membrane vesicles in these experiments suggests the existence of a calcium transfer mechanism in plasma membranes of the adrenal medulla but not adrenal cortex.
To assess whether previously reported ultrastructural alterations of adrenocortical mitochondria induced by the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor PD 132301-2 are accompanied by functional deficits in tissue energy stores, phosphorylated adenine nucleotide levels in guinea pig adrenal cortex were quantitated. Adrenals of male guinea pigs were obtained at 1, 2, 6, or 24 hours after oral administration of 100 mg/kg PD 132301-2 or 0.5% methylcellulose vehicle. In treated animals, ATP levels and ATP/ADP ratios were decreased approximately 50% with concurrent increases in AMP. Calculated energy charge was also decreased; these decreases were maximal by 6 hours. Cholesterol esterification in adrenal cortex was inhibited, resulting in progressive accumulation of free cholesterol up to 3-fold over control by 24 hours, consistent with the ACAT inhibitory activity of the drug. These data suggest that PD 132301-2 distributes to the adrenal cortex where early alterations of tissue bioenergetics occur in a time frame consistent with ultrastructural alterations of mitochondria.
The presence of lipid substances in the rat adrenal cortex was analysed two months after ending a one-month exposure to detergents. An increased quantity of neutral lipids was found throughout the adrenal cortex. An augmented triglyceride content was manifested to a higher degree in adrenocorticocytes. The largest quantity of phospholipids was observed in the adrenal cortex. The changes in the quantity and quality of lipid substances were described, which all testified to a stimulated activity of adrenal gland.
Explore the source record for details and available documents.
The study aimed to compare, by means of stereologic methods, the reactivity of the adrenal cortex of the hamster and the rat to prolonged treatment with 4-aminopyrazolo-(3,4d)pyrimidine (4-APP), a drug reducing hepatic secretion of plasma lipoprotein. Adult female hamsters, intact or cortisone suppressed, were administered i.p. daily with 0.5 mg 4-APP for 5 days while intact female rats received 1 mg of the drug per dose. 4-APP resulted in a loss of body weight, with the more profound effect in the hamster. In the rat 4-APP did not change the adrenal gland weight, the volume of the adrenocortical zones, the average volume of adrenocortical cells and the number of parenchymal cells in the gland. Moreover, serum ACTH and corticosterone levels in the rat remained unchanged. In the intact hamster 4-APP decreased the adrenal gland weight, the volume of the zona fasciculata and enhanced the serum cortisol level. In steroid suppressed hamsters 4-APP lowered the adrenal weight, the volume of fasciculata and reticularis zones, the average volume of the fasciculata cells and the number of parenchymal cells in the gland. These findings may suggest the direct inhibitory effect of low 4-APP doses on the hamster adrenal cortex and clearly demonstrate higher susceptibility of the hamster adrenal cortex, if compared with the rat, to 4-aminopyrazolo-pyrimidine.
PURPOSE: To study the relationship between angiotensin II (AII) receptor occupancy ex vivo in tissues plasma concentration and hypotensive effect of a novel AII receptor antagonist, TH-142177 and losartan in rats. METHODS: At 2, 8 and 24 hr after oral administration of TH-142177 and losartan in rats, AII receptors in myocardium, adrenal cortex and cerebral cortex were determined by radioligand binding assay using [125I]Sar1,Ile8-AII. Plasma concentrations of both drugs and metabolite in rats were also measured using validated HPLC assays. Further, systolic blood pressure (SBP) in conscious renal hypertensive rats treated orally with TH-142177 and losartan were measured by using a tail cuff plethysmographic method. RESULTS: Oral administration of TH-142177 (1.8 and 5.5 micromol/kg) and losartan (6.5 and 21.7 micromol/kg) in rats brought about dose-dependent decreases in [125I]Sar1,Ile8-AII binding sites (Bmax) in myocardium and adrenal cortex. The extent of receptor occupancy by both drugs in adrenal cortex was maximal at 2 hr later but that in myocardium at 8 hr later. Further, the receptor occupancy was more sustained in myocardium than adrenal cortex. The ex vivo binding affinity of TH-142177 for AII receptors in these tissues was roughly three times higher than that of losartan. Also, cerebral cortical [125I]Sar1,Ile8-AII binding was significantly reduced by oral administration of losartan but not by TH-142177. The time course of AII receptor occupancy by both drugs in adrenal cortex appeared to be in parallel with that of their plasma concentrations, while the time course in myocardium correlated with that of their hypotensive effects rather than plasma concentrations. CONCLUSIONS: TH-142177 produced a relatively selective and sustained occupancy ex vivo of AII receptors in myocardium and adrenal cortex of rats with approximately three times greater potency than losartan. Its time course of myocardial receptor occupancy was in parallel with that of hypotensive effect rather than plasma concentration.
Specific corticosterone binding to calf adrenal cortex plasma membrane was measured using the biologically active radioligand [3H]corticosterone. Corticosterone binding was found to be time-dependent, saturable and reversible, and was reduced by more than 70% when membranes were pretreated with proteases. The population of corticosterone binding sites in calf adrenal cortex plasma membrane was homogeneous and displayed the following characteristics: equilibrium dissociation constant Kd = 77 +/- 8 nM and maximum specific binding capacity Bmax = 70,378 +/- 6,385 fmol/mg protein. The relative affinities of several structural analogues of steroids were deduced from competition assays. From these experiments we can conclude that the plasma membrane binding site characterized is selective for corticosterone and progesterone derivatives, and different from nuclear glucocorticoid, mineralocorticoid, estrogen and progestin receptors. Likewise, this corticosterone binding site is independent of mineralocorticoid and Na+, K(+)-ATPase digitalis receptors. From autoradiographic studies we suggest these corticosterone binding sites are located in the whole adrenal cortex.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The presence and localization of c-fos-like immunoreactivity in the rat adrenal cortex has been demonstrated by immunocytochemical methods at both light and electron microscopic level. C-fos-like immunoreactivity was detected in the zona fasciculata and the zona reticulata, but not in the zona glomerulosa. Ultrastructurally, all products of c-fos-like immunoreaction were localized exclusively in the regions associated with the euchromatin in the nucleus of the immunoreactive cells. Moreover, a higher density of the immunoreactive cells in the adrenal cortex of pregnant rats was found with quantitative immunocytochemistry as compared to the non-pregnant. The characteristic zonation of c-fos-like immunoreactivity in the adrenal cortex suggest that the c-fos protein is involved in the normal function of the glucocorticoid-producing cells of mammalian adrenals. The numerical increase in the immunoreactive cells in pregnant rats implies that basal expression of the c-fos-like protein may vary with the functional state of the cortical cells.
Adrenal and serum corticosterone concentrations, cholesterol association with adrenal cortical cytochrome P-450scc (the cytochrome P-450 catalyzing the conversion of cholesterol to pregnenolone), and adrenal cortical activities of cholesteryl ester hydrolase, acyl-CoA:cholesterol acyltransferase, and cholesterol side-chain cleavage have been determined at various times following stress in female rats. The paramount importance of cholesterol side-chain cleavage activation in the response to stress at the low point of the circadian rhythm is confirmed. At the high point of the circadian rhythm, there is evidence that the provision of free cholesterol for the cytochrome P-450scc enzyme system may also be controlled. The data support a coordinate action of ACTH and pro-gamma-melanotropin in controlling cholesterol metabolism in the adrenal cortex following stress.