Effects of prolonged treatment with cyanoketone on the zona fasciculata of rat adrenal cortex

Summary We have examined IgG Fc receptor (FcR) activity of human and rabbit arachnoid granulations and leptomeninges using antibody (IgG)-coated erythrocytes (EIgG), covalently crosslinked IgG dimers, trimers and oligomers, immune complexes, aggregated Fc fragments and a monoclonal anti-human neutrophil Fc receptor antibody, 3G8. EIgG bound specifically to cells of the leptomeninges and arachnoid granulations; uncoated erythrocytes, F(ab) ₂-coated, or IgM-coated erythrocytes failed to bind. The specificity of this interaction was demonstrated by inhibition studies. Monomeric IgG and Fc fragments blocked EIgG adherence, whereas bovine serum albumin (BSA), Fab fragments of IgG and the monoclonal anti-neutrophil FcR antibody failed to inhibit EIgG adherence. Monomeric IgG inhibited FcR function in a dose-dependent fashion; maximal inhibition was achieved at 1.7 × 10^-5M IgG, indicating a relatively low avidity receptor. Oligomers of IgG inhibited EIgG adherence more effectively and inhibition was directly related to oligomer size. Additionally, these tissues were positive for specific and non-specific esterases. These studies suggest that the CSF pathway from the perivascular spaces to the arachnoid granulations plays a protective role in the clearance of IgG and IgG immune complexes in infections and immune-mediated disorders.Work partially supported by PHS Grant #Ca 38055, National Cancer InstituteWork primarily supported by the Veterans Administration Merit Program     

Effects of streptozotocin-induced experimental diabetes on the morphology and function of the zona fasciculata of rat adrenal cortex

The effects of a severe streptozotocin (STZ)-induced diabetes on the morphology and function of the adrenal zona fasciculata were examined in rats with intact or pharmacologically interrupted hypothalamic-hypophyseal-adrenal axis. In animals with an intact hypothalamic-hypophyseal axis, STZ-diabetes induced hypertrophy of the cells of the zona fasciculata and a rise in the plasma corticosterone concentration. Conversely, in rats in which the hypothalamic-hypophyseal axis had been interrupted, experimental diabetes provoked atrophy of the zona fasciculata cells, and a lowering in the plasma corticosterone level. The effects of STZ-diabetes were completely reversed by insulin infusion in both groups of rats. The hypothesis is discussed that the chronic lack of insulin may directly inhibit the growth and steroidogenic capacity of the rat zona fasciculata and that this effect of experimental diabetes may be masked in rats with an intact hypothalamic-hypophyseal axis by the concurrent enhancement of ACTH release due to chronic stress resulting from the metabolic consequences of prolonged diabetes.     

Effects of the infusion with ACTH or CRH on the secretory activity of rat adrenal cortex

Six-hour infusion with ACTH or CRH induced a dose-dependent rise in the plasma concentrations of ACTH, corticosterone (B) and aldosterone (A). Positive linear correlations between the plasma levels of ACTH and B or A were found in both ACTH-or CRH-infused animals. Regression curves for B were similar in both groups of animals, while the regression line for A was significantly (P less than 0.05) steeper in CRH-than in ACTH-treated rats. These findings suggest that, in the rat, the mechanism underlying the CRH-induced stimulation of A secretion does not exclusively involve the enhancement of ACTH release.     

Effects of prolonged treatment with adrenocorticotropin on the morphology and function of rat adrenocortical autotransplants.

Regenerated adrenocortical nodules were obtained by implanting in the musculus gracilis of rats fragments of the capsular tissue of their excised adrenal glands. Five months after operation, transplanted rats showed a slightly elevated blood concentration of adrenocorticotropin (ACTH), a moderately reduced plasma level of corticosterone (PBC) and a very low concentration of circulating aldosterone (PAC). Regenerated nodules were well encapsulated, and from the connective capsule some septa dipped into the parenchyma. Subcapsular-outer (OZ) and inner (IZ) cells were similar to those of the zona fasciculata/zona reticularis (ZF/ZR) of the normal gland; juxta-septal (JZ) cells resembled those of the zona glomerulosa (ZG). Prolonged (14 days) ACTH infusion normalized PBC and caused a conspicuous hypertrophy of transplanted tissue, which was coupled with a marked hypertrophy of ZF/ZR-like OZ and IZ cells and a notable rise in the basal in vitro production of corticosterone. Conversely, ACTH infusion strikingly lowered PAC, reduced the number of ZG-like JZ cells, and decreased both basal and stimulated secretion of 18-hydroxylated steroids by transplants in vitro.     

Effects of prolonged sodium restriction on the morphology and function of rat adrenocortical autotransplants

Summary Regenerated adrenocortical nodules were obtained by implanting fragments of the capsular tissue of excised adrenal glands into the musculus gracilis of rats (Belloni et al. 1990). Five months after the operation, operated rats showed a normal basal blood level of corticosterone, but a very low concentration of circulating aldosterone associated with a slightly increased plasma renin activity (PRA). Regenerated nodules were well encapsulated and some septa extended into the parenchyma from the connective-tissue capsule. The majority of parenchymal cells were similar to those of the zonae fasciculata and reticularis of the normal adrenal gland, while zona glomerulosa-like cells were exclusively located around septa (juxta-septal zone; JZ). In vitro studies demonstrated that nodules were functioning as far as glucocorticoid production was concerned, while mineralocorticoid yield was very low. Prolonged sodium restriction significantly increased PRA and plasma aldosterone concentration, and provoked a marked hypertrophy of JZ, which was due to increases in both the number and average volume of JZ cells. Accordingly, the in vitro basal production of aldosterone and other 18-hydroxylated steroids was notably enhanced. The plasma level of corticosterone, as well as zona fasciculata/reticularis-like cells and in vitro production of glucocorticoids by regenerated nodules were not affected. These findings, indicating that autotransplanted adrenocortical nodules respond to a prolonged sodium restriction similar to the normal adrenal glands, suggest that the relative deficit in mineralocorticoid production is not due to an intrinsic defect of the zona glomerulosa-like JZ, but is probably caused by the impairment of its adequate stimulation under basal conditions. The hypothesis is advanced that the lack of splanchnic nerve supply and chromaffin medullary tissue in regenerated nodules may be the cause of such an impairment.     

Effects of a prolonged treatment with aminoglutethimide on the zona fasciculata of rat adrenal cortex: A morphometric investigation

Summary The effects of a 7-day administration of aminoglutethimide (AG) on the adrenal zona fasciculata were examined in normal and dexamethasone/ACTH-treated rats. There was a 70–74% decrease in the concentration of corticosterone in blood, but no conspicuous qualitative changes suggesting cell degeneration occurred. Morphometry showed that AG induced a significant hypertrophy of the zona fasciculata and its parenchymal cells only in normal animals, which was due to an increase in the volume of the mitochondrial compartment and to proliferation of the smooth endoplasmic reticulum. This response to AG was considered to be non-specific and mediated by the enhanced secretion of ACTH following the decrease in the blood level of corticosterone. AG administration significantly increased the volume of the lipid-droplet compartment and the number of intramitochondrial lipid-like inclusions in both groups of animals. These changes were interpreted as the morphological counterpart of the AG-induced block of cholesterol utilization in steroid synthesis.     

The effects of ageing on the morphology and function of the zonae fasciculata and reticularis of the rat adrenal cortex

Summary The morphological counterpart of the well-known age-dependent marked impairment of glucocorticoid secretion of rat adrenals was investigated by use of morphometric techniques. For this purpose 4-, 8-, 16- and 24-month-old rats were studied. Despite the notable lowering of both basal and ACTH-stimulated production of corticosterone by collagenase-dispersed inner adrenocortical cells, ACTH and corticosterone plasma concentrations displayed significant increases with ageing. Zona fasciculata (ZF) and zona reticularis (ZR) showed a notable hypertrophy in aged rats, which was due to rises in both the average volume and number of their parenchymal cells. The hypertrophy of ZF and ZR cells was in turn associated with increase in the volume of the mitochondrial compartment and proliferation of smooth endoplasmic reticulum, i.e., the two organelles involved in steroid-hormone synthesis. All these morphologic changes, conceivably due to the chronic exposure to high levels of circulating ACTH, are interpreted as a response enabling ZF and ZR to compensate for their age-dependent lowering in glucocorticoid secretion. Stereology also demonstrated that ZF and ZR cells underwent a striking age-related lipid-droplet repletion. Lipid droplets are the intracellular stores of cholesterol esters, the obligate precursors of steroid hormones in rats. This finding is in keeping with the contention that the mechanism underlying the age-dependent decline in rat-adrenal glucocorticoid secretion mainly involves impairments of the utilization of intracellular cholesterol previous to its intramitochondrial transformation to pregnenolone.     

Age-related changes in the morphology and function of the zona glomerulosa of the rat adrenal cortex

The age-related changes in the morphology and function of rat adrenal zona glomerulosa (ZG) were investigated by coupled stereological and radioimmunological techniques. For this purpose 4-, 8-, 16- and 24-month-old rats were studied. Aging caused a notable lowering in the plasma aldosterone concentration and a marked decrease in both basal and ACTH- or angiotensin II (ANG-II)-stimulated secretion of collagenase-dispersed ZG cells. Plasma renin activity (PRA) underwent an age-dependent decrease, while the plasma level of ACTH displayed a significant rise. ZG and its parenchymal cells did not evidence any age-related morphologically demonstrable alteration in their growth, nor ZG cells showed any marked ultrastructural change, with the exception of a severe lipid-droplet repletion. This last finding is in keeping with the aging-induced decrease in the secretory activity of ZG cells, inasmuch as lipid droplets are the intra-cellular stores of cholesterol esters, the obligate precursors of steroid hormones in rat adrenals. ACTH and ANG-II are well known to be involved in the maintenance of the growth of rat ZG; thus, the combined impairment of ANG-II production (as evidenced by PRA lowering) and increase in ACTH secretion may maintain unchanged ZG growth during aging.     

Characterisation of endothelin-1-related protein in human adrenal cortex and in cortical lesions

 Endothelin (ET)-1 is a 21-amino acid peptide with potent vasopressor and vasoconstrictive properties. Biochemical studies suggest that this peptide occurs in the adrenal cortex, where it appears to influence steroid hormone production and catecholamine release. Concomitant with our previous immunohistological study, we found ET-1 immunoreactive (IR) cells in human adrenal cortex and cortical neoplasms, but not in the medulla. These ET-1 IR cells were numerous in adenomas, but were seen only occasionally in some of the carcinomas. In the present study, the ET-1 IR protein was extracted from normal (n=5) and hyperplastic (n=3) human cortex as well as from cortical adenomas (n=10) and carcinomas (n=5). Its molecular weight, determined by SDS-polyacrylamide gel electrophoresis and immunoblotting, was 9 kD, which is lower than that of prepro-ET-1 (21 kD), but larger than that of pre-ET-1 (4.3 kD) and ET-1 (2.5 kD). The normal cortical specimens, hyperplasias, adenomas and three of the five carcinomas all contained this distinct band. The two carcinomas lacking it were associated with Conn’s syndrome. The protein may constitute a protein not previously described, but further studies are needed to determine its complete structure. Accepted: 18 August 1998     

Effects of microwaves on the adrenal cortex

Six-hundred-and-one male Long-Evans rats were used to study the effect of microwaves on adrenocortical secretion. Power density ranged from 0.1 to 55 mW/cm2 (SAR 0.02 to 11 W/kg). The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Serum corticosterone (CS) concentration was used as an index of adrenocortical function. Ten different exposure protocols were used to identify confounding factors influencing the sensitivity of adrenal cortex to microwave exposure. Increases in CS concentration were proportional to power density or colonic temperature and inversely proportional to the baseline CS. Increased CS concentration was never observed without increased colonic temperature and was not persistent 24 h after exposure. Acclimation (reduction in magnitude of response) could be noted after the tenth exposure. Facilitated heat loss attenuated the magnitude of CS increases by limiting the degree of hyperthermia. Ethanol enhanced the hyperthermic response and desensitized the adrenal response to microwave hyperthermia by increased baseline CS. Ether stimulated adrenal secretion irrespective of previous microwave exposure or adrenal stimulation induced by microwaves. Minor inhibition was also noted occasionally as decreased CS concentration at lower intensity (less than 20 mW/cm2) and decreased postexposure urinary CS excretion at 40 mW/cm2. Adrenal stimulation required minimally a 20 mW/cm2 (4 W/kg) or 0.7 degrees C increase in colonic temperature. An SAR lower than 4 W/kg may stimulate adrenal secretion by potentiating the hyperthermic effect if the ambient temperature is well above 24 degrees C.     

Evidence that prolonged alpha-MSH infusion enhances the steroidogenic capacity of rat adrenal zona glomerulosa in vivo

Prolonged infusion with 120 micrograms/kg/day alpha-MSH significantly increased basal plasma level of aldosterone in the rat, as well as raised the acute aldosterone response to a bolus administration of a high dose of ACTH or angiotensin II. These findings suggest that chronic alpha-MSH treatment stimulates the steroidogenic capacity of rat zona glomerulosa.