Biomedical subjects

P Rebuffat

Publications and source records attributed to P Rebuffat.

At least 55 records · Page 3Linked to original sources

PubMed1992

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.

Aging↗

PubMed1992

Morphology and functional responses of isolated inner adrenocortical cells of rats infused with interleukin-beta.

The effects of the prolonged infusion with interleukin-1 beta (IL-1 beta) (20 pM.kg-1.min-1) on the function and morphology of the isolated inner cells of the rat adrenal cortex were investigated. After 3 and 5 days of IL-1 beta infusion, the level of circulating ACTH was below the control level, while the plasma concentration of corticosterone was strikingly elevated. After 5 days of infusion, isolated inner adrenocortical cells showed an enhanced basal and ACTH-stimulated corticosterone secretion, and showed a conspicuous hypertrophy. The acute exposure to IL-1 beta 10(-6) M did not affect the secretory activity of dispersed cell from either control or IL-1 beta-infused rats. These findings indicate that the prolonged exposure to high levels of circulating IL-1 beta, like those occurring during chronic inflammatory diseases, is able to enhance the growth and steroidogenic (glucocorticoid) capacity of the rat inner adrenocortical zones. Moreover, they suggest that the mechanism underlying this adrenocorticotrophic effect of IL-1 beta does not involve either a stimulation of the hypophyseal ACTH release or a direct stimulatory effect of monokine on adrenocortical cells. It is suggested that IL-1 beta may activate an intra-adrenal paracrine regulatory mechanism.

Adrenal Cortex↗

PubMed1991

Effects of the hypocholesterolemic drug, 4-aminopyrazolo (3,4-d) pyrimidine (4-APP), on the hamster adrenal cortex. An ultrastructural and functional study.

The aim of this study was to gain insight into the effects of 4-aminopyrazolo(3,4-d)pyrimidine (4-APP), a hypocholesterolemic drug, on the adrenal cortex of the hamster, representing an animal species in which steroidogenesis primarily relies on utilization of cholesterol synthesized de novo in the gland. 4-APP administration (1.5 mg/animal day for 3 days) to intact or dexamethasone-suppressed hamsters resulted in a marked proliferation of adrenocortical cells. However, the volume of parenchymal cells was unchanged in intact animals and lowered in the zona glomerulosa (ZG) and zona reticularis (ZR) of dexamethasone-administered hamsters. In both groups of animals, 4-APP strikingly increased the volume of the lipid-droplet compartment and markedly reduced the surface area of smooth endoplasmic reticulum in ZF cells, without significantly affecting the volume of the mitochondrial compartment and the surface area of mitochondrial cristae. These morphologic changes displayed no evident correlation with adrenal cortisol content and secretion. Since most of the 4-APP-induced changes were not prevented by dexamethasone, it seems legitimate to suggest that they could mainly depend on a direct effect of 4-APP on the hamster adrenocortical cells.

Adenine↗

PubMed1991

Effects of prolonged cysteamine administration on the rat adrenal cortex: evidence that endogenous somatostatin is involved in the control of the growth and steroidogenic capacity of zona glomerulosa.

A week daily administration of cysteamine (CYS, 300 mg kg-1) lowered plasma aldosterone concentration in rats, without affecting PRA, kalaemia and the plasma levels of ACTH and corticosterone. Prolonged CYS treatment caused a notable hypertrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells, without inducing any apparent change in zona fasciculata morphology. Isolated ZG cells from CYS-treated rats evidenced a notable enhancement in their basal and maximally-stimulated productions of aldosterone and corticosterone. All these effects of chronic CYS administration were completely reversed by the simultaneous infusion of rats with somatostatin (SRIF, 12 micrograms kg-1 h-1). CYS exposure was not found to directly affect the secretory activity of isolated ZG cells from normal rats. Since CYS is known to be a specific depletor of SRIF in different organs of rats, these findings suggest that endogenous SRIF may be involved in the modulation of ZG function.

Adrenal Cortex↗

PubMed1991

A coupled morphological and biochemical study on the cellular localisation of the intra-adrenal renin granules in rats.

The effects of prolonged (3-week) sodium restriction on the rat zona glomerulosa (ZG) were investigated by ultrastructural stereological and biochemical techniques. The plasma level of aldosterone was increased, and this was coupled with a notable decrease in the volume density (Vv, microns 3/100 microns 3 of cell) of lipid droplets in ZG cells. Renin-like activity (RLA) underwent a significant rise in ZG, and Vv of dense bodies significantly rose in ZG cells. Since RLA and dense-body Vv displayed a highly significant linear correlation (r = 0.884; n = 22, P less than 0.01), the hypothesis is advanced that part of the dense bodies may be granules of prorenin or renin, and that ZG parenchymal cells are directly involved in the intra-adrenal renin production.

Aldosterone↗

PubMed1991

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.

Adrenal Cortex↗

PubMed1990

Effects of prolactin on the morphology and function of rat Leydig cells: short-term versus long-term administration.

The bolus administration of prolactin (PRL) to adult rats did not cause any apparent change in the basal and luteinizing hormone (LH)-stimulated blood levels of testosterone (as estimated by radioimmune assay). Prolonged PRL infusion did not affect either basal testosterone plasma concentration or the morphology of Leydig cells (as evaluated by electron microscopy and stereology). Conversely, prolonged PRL treatment notably increased the gonadotrophic effects of chronic LH administration; this mainly consisted of a rise in the blood concentration of testosterone and a conspicuous hypertrophy of Leydig cells. The LH-induced increase in the volume of Leydig cells was the result of an increase in the volumes of all the organelles involved in steroid synthesis (i.e., smooth endoplasmic reticulum, peroxisomes and mitochondria). However, the trophic effects of PRL infusion exclusively concerned smooth endoplasmic reticulum and peroxisomes. In the light of these findings, the hypothesis is advanced that the mechanism underlying the gonadotrophic action of PRL involves an enhancement of the endogenous cholesterol synthesis, which could provide an abundance of precursors for testosterone synthesis, the post-cholesterol steps of which, in turn, would be exclusively controlled by LH.

Animals↗

PubMed1990

Streptozotocin-induced experimental diabetes causes a time-dependent inhibition of growth and steroidogenic capacity of rat adrenal zona glomerulosa.

The effects of streptozotocin-induced experimental diabetes on the morphology and secretory activity of the zona glomerulosa were studied in rats whose hypothalamo-hypophyseal-adrenal axes and renin-angiotensin systems had been pharmacologically interrupted by the simultaneous administration of dexamethasone-captopril and maintenance doses of ACTH-angiotensin II. The animals were examined 7, 14, 21, and 28 days after diabetes induction, which was evidenced by conspicuous hyperglycemia. Experimental diabetes caused notable atrophy of the zona glomerulosa and its cells, along with a significant decrease in both basal and angiotensin II-stimulated plasma aldosterone concentration. There was a positive linear correlation between all these changes and the number of days elapsed after streptozotocin administration. These data indicate that experimental diabetes exerts a profound time-dependent direct inhibition of rat zona glomerulosa. The hypothesis is advanced that the chronic lack of insulin that occurs in rats treated with streptozotocin, may depress de novo synthesis of structural and enzymatic proteins in zona glomerulosa cells and reduce their growth and steroidogenic machinery.

Adrenal Cortex Hormones↗

PubMed1990

Morphology and functional responses of isolated zona glomerulosa cells of streptozotocin-induced diabetic rats.

Streptozotocin-induced diabetes significantly decreased plasma aldosterone concentration in rats whose renin-angiotensin system had been pharmacologically interrupted. Isolated zona glomerulosa cells showed a marked atrophy, coupled with a reduced basal secretion of aldosterone and corticosterone. The secretory response to the three main physiological stimuli (ACTH, angiotensin II and potassium) was also notably impaired. The hypothesis is advanced that the chronic lack of insulin may directly impair the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

Adrenocorticotropic Hormone↗

PubMed1990

Effects of acute and chronic treatments with atrial natriuretic factor (ANF) on the Leydig cells of the rat testis.

Acute ANF bolus administration (40 micrograms.kg-1) did not affect secretory activity and morphology of rat Leydig cells. Prolonged (7-day) ANF infusion (20 micrograms.kg-1.h-1), on the contrary, elevated both basal and hCG-stimulated testosterone blood concentration, and caused a notable hypertrophy of rat Leydig cells. Leydig-cell hypertrophy was due to increases in the volume of all the organelles involved in cholesterol and testosterone synthesis (i.e. mitochondria, smooth endoplasmic reticulum and peroxisomes). These findings suggest that ANF, when chronically administered, is able to stimulate the growth and steroidogenic capacity of rat Leydig cells.

Animals↗

PubMed1990

Investigations on the morphology and function of adrenocortical tissue regenerated from gland capsular fragments autotransplanted in the musculus gracilis of the rat.

This paper describes the function and morphology of regenerated adrenocortical nodules obtained by implanting, in the musculus gracilis of rats, several (n = 6-7) fragments of the capsular tissue of their excised adrenal glands. Four months after the operation, each bilaterally adrenalectomized rat developed six or seven well encapsulated adrenocortical nodules about 2-3 mm in diameter and always lacking chromaffin cells, and displayed almost complete normalization of basal and stimulated blood levels of corticosterone, but not of aldosterone. In vitro study showed that regenerated nodules were well functioning as far as glucocorticoid production was concerned. Accordingly, electron microscopy and stereology indicated that the majority of the parenchymal cells (independently of their location in the outer subcapsular, middle, or inner portions) closely resembled those of the zonae fasciculata/reticularis of the adrenal gland of age-matched sham-operated rats. By contrast, regenerated nodules evidenced a relative impairment in aldosterone secretion, and this was coupled with the presence of only a few zona glomerulosa-like cells. Such cells were grouped in small islets located near the few connective trabeculae detaching from the capsule, and autoradiography showed that they were the only parenchymal elements of the nodule able to bind [125I]angiotensin-II. The possibility is suggested that the paucity of zona glomerulosa-like cells in regenerated nodules could be ascribed to the absence of zona medullaris, which is currently thought to exert a paracrine control on the growth and secretion of zona glomerulosa in the rat adrenal glands.

18-Hydroxycorticosterone↗

PubMed1990

Cellular responses of the rat adrenal zona fasciculata to acute ACTH stimulation: a morphometric study.

Long-term ACTH-stimulation of steroidogenesis in the rat adrenal cortex results in time-dependent increases in the surface area per cell of smooth endoplasmic reticulum and mitochondrial cristae. As the morphological responses to short-term ACTH stimulation have not been described, we undertook morphometric analyses of the effects of acute (10 min) ACTH stimulation of rat adrenocortical cells in vivo as they may be expressed in the mitochondria and the smooth endoplasmic reticulum. Six young male Wistar rats were allocated to each of four groups: 1. normal controls; 2. ACTH-treated normal rats; 3. Dexamethasone-inhibited; 4. ACTH-treated Dexamethasone-inhibited. As judged by the radio-immunoassay of trunk blood, levels of ACTH, 11-deoxycorticosterone and corticosterone were appropriate to the treatment state. ACTH activation resulted in no changes in the smooth endoplasmic reticulum; but the mitochondrial inter-membrane space was significantly increased over that of the contrasted pair. The inter-membrane space in the dexamethasone-inhibited rats was significantly less than that of all other groups. No responses to ACTH-activation were shown by the intra-cristal or matrix volumes of the mitochondria. The increased inter-membrane space appears to be caused by a decrease in the surface area of the inner mitochondrial membrane. The significance of these intra-mitochondrial changes to the rate-limiting step of steroidogenesis is discussed.

Adrenocorticotropic Hormone↗

PubMed1990

Stereological and functional investigations on isolated adrenocortical cells. III. Zona glomerulosa cells of chronically ACTH-treated rats.

Prolonged (5 day) treatment of rats with high doses of ACTH caused a significant reduction in the plasma concentration of aldosterone and a notable rise in that of corticosterone. Outer subcapsular (zona glomerulosa [ZG]) adrenocortical cells were isolated, and their morphology and secretory activity was investigated. ACTH pretreatment induced a marked hypertrophy of ZG cells which was coupled with significant increases in the volume of the mitochondrial compartment and in the surface area per cell of mitochondrial cristae and AER tubules, as well as with a striking lipid droplet depletion. Mitochondrial cristae were found to change from a tubulo-laminar to a tubulo-convolute configuration. Despite their hypertrophy, ZG cells from ACTH-pretreated rats displayed a conspicuous decrease in both basal and stimulated overall production of post-pregnenolone steroids, which was ascribed to the depletion of their stores of steroid hormone precursors (i.e. cholesterol and cholesterol esters contained in the lipid droplets). However, both basal and stimulated secretion of aldosterone was doubled, suggesting that chronic ACTH treatment induces in ZG cells an increased availability of monoxygenase II, the enzyme involved in the transformation of 18-hydroxycorticosterone into aldosterone. In the light of these findings, the drop in the plasma level of aldosterone observed in rats after prolonged treatment with ACTH is assumed to be due to an enhanced metabolism of aldosterone, possibly at the hepatic level.

18-Hydroxycorticosterone↗

PubMed1989

Gestational changes in hamster adrenal cortex: morphometric and ultrastructural stereologic studies.

In the hamster, the weight of the adrenal glands increases during the course of gestation, with the highest value at day 5. In comparison to non-pregnant control animals, there were no changes in the volume of the zona glomerulosa (ZG) and zona fasciculata (ZF), while the volume of the zona reticularis (ZR) increased notably. The average volume of ZG-cells rose at day 5 of pregnancy and thereafter gradually decreased to that of control hamsters. A marked drop in the volume of ZF-cells was seen at days 5 and 10 of pregnancy, whereas at day 15 the cells were larger than in controls. At day 5 of pregnancy, a conspicuous increase in the cell volume was found in ZR, followed by lower values at day 10 and again higher than in control hamsters at day 15. The total number of parenchymal cells in hamster adrenal cortex increased at day 10 of gestation, then underwent a marked decrease, reaching the control value at the final day of pregnancy; this drop was mainly due to a reduction in the number of ZF-cells. The changes in the cell volume were paralleled by rather proportional changes in the volume of the mitochondrial compartment and in the quantity of smooth endoplasmic reticulum. The volume of the lipid-droplet compartment significantly rose in the course of gestation in both ZF- and ZR-cells. The cortisol output by adrenal homogenates gradually decreased during pregnancy.

Adrenal Cortex↗

PubMed1989

Stereological and functional investigations on isolated adrenocortical cells: zona fasciculata/reticularis cells of chronically ACTH-treated rats.

The morphology and function of isolated inner (zona fasciculata/reticularis) adrenocortical cells of rats pretreated with ACTH for 3, 6, 9 or 12 days were investigated. ACTH treatment induced a notable time-dependent enhancement in the steroidogenic capacity (corticosterone production) and growth of inner cells. The volumes of cells, mitochondrial compartment, membrane space [the cellular space occupied by smooth endoplasmic reticulum (SER) membranes] and lipid-droplet compartment, as well as the surface area of mitochondrial cristae and SER tubules, were increased in relation to the duration of ACTH pretreatment, and showed a highly significant positive linear correlation with both basal and stimulated corticosterone production. The acute exposure of isolated cells to ACTH provoked a striking lipid-droplet depletion, the extent of which was linearly and positively correlated with stimulated corticosterone secretion. The hypertrophy of the mitochondrial compartment and SER are interpreted as the morphological counterpart of the enhanced steroidogenic capacity of inner adrenocortical cells, inasmuch as the enzymes of steroid synthesis are located in these two organelles, and it is well known that chronic ACTH exposure stimulates the de novo synthesis of many of them in vivo. The rise in the number of lipid droplets, in which cholesterol is stored, is interpreted as being due to the fact that, under chronic ACTH treatment, the processes leading to cholesterol accumulation in adrenocortical cells (exogenous uptake and endogenous synthesis) exceed those of its utilization in basal steroid secretion. Cholesterol accumulated in lipid droplets as a reserve material may be rapidly utilized after acute ACTH exposure to meet the needs of the enhanced steroidogenic capacity of adrenocortical cells.

Adrenal Cortex↗

PubMed1989

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.

Adrenal Cortex↗

PubMed1989

Further studies on the involvement of dopamine and somatostatin in the inhibitory control of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

Prolonged (12-day) sodium restriction increased basal plasma concentration of aldosterone and provoked a notable hypertrophy of the zona glomerulosa and its cells in rats. A 7-day infusion of dopamine or somatostatin, at a rate which was found to exert a maximum inhibition of aldosterone secretion in 12 h, only partially reversed the effects of sodium deprivation. However, the combined administration of these two molecules not only completely annulled the effects of sodium restriction, but also lowered plasma aldosterone concentration and the volumes of the zona glomerulosa and its cells below the values found in rats fed a normal diet. These findings confirm the contention that dopamine and somatostatin are both involved in the negative control of the growth and steroidogenic capacity of the rat zona glomerulosa, and suggest that different mechanisms underlie the antiadrenoglomerulotrophic action of these molecules.

Aldosterone↗

PubMed1989

Effects of prolonged cyclosporine-A treatment on the morphology and function of rat adrenal cortex.

The effects of prolonged (30 day) treatment with daily therapeutical doses of cyclosporine A (CSA) (20 mg/kg) on the function and morphology of adrenal cortex were studied in adult male rats. CSA-treated animals developed a notable hypertension, along with a striking rise in PRA, which was not coupled with significant changes in the plasma concentrations of aldosterone and corticosterone (hyperreninemic hypoaldosteronism). Morphometry showed that zona glomerulosa (ZG) and zona fasciculata, and their parenchymal cells were atrophic. Isolated capsular (ZG) and inner (zona fasciculata/reticularis) cells displayed reduced basal and stimulated secretory responses. However, while the response of ZG cells to angiotensin II was almost completely suppressed (96%), basal steroid secretion of isolated cells, as well as the aldosterone and corticosterone response of ZG cells to potassium and ACTH, and corticosterone production of inner cells in response to ACTH were decreased by only about 30-40%. The hypothesis is advanced that CSA exerts a dual effect on rat adrenal cortex: 1) a general inhibitory effect on the growth and steroidogenic capacity of adrenocortical cells, which manifests itself only after very prolonged treatment and may be caused by an impairment of protein synthesis; and 2) an acute effect involving the specific blockade of the angiotensin-II-induced stimulation of the secretory activity of ZG cells.

Adrenal Cortex↗