An ultrastructural stereological study of accessory adrenocortical glands in bilaterally adrenalectomised rats.
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Journal Article↗
Biomedical subjects
P Rebuffat
Publications and source records attributed to P Rebuffat.
Effects of 4-aminopyrazolo (3,4-d) pyrimidine on rat hepatocytes: an ultrastructural morphometric study.
The prolonged administration of the hypolipidemic drug 4-aminopyrazolo (3,4-d) pyrimidine (4APP) induced conspicuous morphological changes in rat hepatocytes, which are clearly demonstrated by stereology. We observed a significant decrease in the rough endoplasmic reticulum, and an accumulation of lipid droplets, which was coupled with a comparable rise in the hepatic concentrations of total cholesterol and triglycerides. These changes were interpreted as the expression of the 4APP-provoked impairment of the synthesis of the polypeptide chains of lipoproteins and of the consequent suppression of the assembly of lipid molecules in exportable lipoproteins. We also noted a neto lowering in smooth endoplasmic reticulum and peroxisomes, a decrease which was hypothesized to be the morphological counterpart of a reduced de novo cholesterol synthesis, due to the 4APP-induced rise in the intracellular cholesterol concentration.
Adenine↗
A morphometric study of the reversal of ACTH-induced hypertrophy of rat adrenocortical cells after cessation of treatment.
The effect of a prolonged (7-day) ACTH administration on rat zona fasciculata cells and its reversal after cessation of treatment was investigated by morphometry. ACTH treatment caused a notable cell hypertrophy, which was mainly due to the increase in the volume of the mitochondrial compartment and to smooth endoplasmic reticulum (SER) proliferation, and a conspicuous rise in the basal level of corticosterone. After cessation of ACTH administration, rat zona fasciculata cells underwent a time-dependent atrophy, so that after 5 days they resembled those of control animals, and the blood concentration of corticosterone reverted to the base-line value. The cell atrophy was provoked by the decrease in the volumes of the mitochondrial compartment and SER, and was associated with a striking time-dependent accumulation of dense bodies. Stereology demonstrated that during the first two days after ACTH withdrawal the decrease of SER prevailed over that of the mitochondrial compartment, while the reverse occurred during the remaining three days. The increase in the volume of dense-body compartment, though largely due to the accumulation of residual bodies, was mainly coupled with a rise in the volume of the microautophagic-vacuole compartment during the first two days after ACTH cessation and with an increase in that of the macroautophagic-vacuole compartment during the following three days. The hypothesis is advanced that both micro- and macroautophagy play a role in the reversal of ACTH-induced hypertrophy of rat zona fasciculata cells after cessation of treatment, the first process being mainly involved in the elimination of SER, and the second one in the degradation of mitochondria.
Adrenocorticotropic Hormone↗
Stereological and functional investigations on isolated adrenocortical cells. I. Adrenocortical cells of normal adult rats.
The function and morphology of isolated rat adrenocortical cells were investigated. Capsular (zona glomerulosa) cells secreted aldosterone, progesterone and small amounts of corticosterone; inner (zonae fasciculata and reticularis) cells produced corticosterone and progesterone. ACTH (10(-8) M) exposure caused a striking rise in aldosterone and corticosterone secretion by capsular cells, and in corticosterone release by inner cell preparations; simultaneously, progesterone secretion was significantly reduced. Capsular and inner cells possessed an average volume of 500 and 1250 micron 3, and ultrastructural qualitative and quantitative (stereological) features closely resembling those of zona glomerulosa and zona fasciculata-reticularis cells in situ, respectively. ACTH exposure caused a notable lipid-droplet depletion in both types of isolated cells.
Adrenal Cortex↗
A stereologic study of the granule population of rat atrial myoendocrine cells: effects of chronic water/sodium restriction and acute water/sodium load.
The effects of chronic water/sodium restriction and acute water/sodium load on the "specific granule" population of rat atrial cardiocytes were investigated by stereology. The volume density (Vv) of atrial granules, which contain atrial natriuretic peptide (ANP), displayed a 135%-rise in water/sodium-restricted animals. The injection of 2.5 ml of isotonic saline to water/sodium-restricted rats provoked a striking degranulation of atrial myoendocrine cells (Vv of granules decreased by about 31%). The administration of an equal volume of hypertonic (5%) saline caused a more pronounced effect (Vv decreased by about 51%). These findings are in agreement with the view that chronic water/sodium restriction blocks the exocytotic release of atrial granules, without lowering the rate of their production. Moreover, they suggest that not only blood volume expansion, but also sodium ions can be a potent stimulating factor of ANP release.
Animals↗
Morphological and functional responses of rat Leydig cells to a prolonged treatment with human chorionic gonadotropins.
The morphological and functional responses of rat Leydig cells to a 3- and 6-day treatment with human chorionic gonadotropins (hCG) (10 IU/kg/day) were investigated by morphometric and radioimmunological techniques. hCG-administration induced a notable time-dependent enhancement in the steroidogenic capacity and growth of Leydig cells; this last was almost exclusively due to hypertrophy (and not to hyperplasia). The volume of mitochondrial and peroxisome compartments, as well as the surface area per cell of mitochondrial cristae and smooth endoplasmic reticulum (SER) were significantly increased after hCG treatment, and showed a highly significant positive linear correlation with both basal and stimulated testosterone production by isolated Leydig cells of the contralateral testis. Also the volume of nuclei and lipid-droplet compartment and the surface area per cell of Golgi apparatus displayed a notable hCG-induced rise, but they did not correlate with testosterone secretion. These findings suggest that, in addition to mitochondria and SER, in which the enzymes of steroid synthesis are located, peroxisomes are also specifically involved in the secretory activity of rat Leydig cells.
Animals↗
Effects of mevinolin, an inhibitor of cholesterol synthesis, on the morphological and functional responses of rat adrenal zona fasciculata to a prolonged treatment with 4-aminopyrazolo-pyrimidine.
Rat adrenocortical cells are almost completely dependent upon the continuous supply of cholesterol derived from serum lipoproteins. However, a prolonged (5-day) administration of 4-aminopyrazolo-pyrimidine (4-APP), a potent hypocholesterolaemic drug, though provoking a notable decrease in the intra-adrenal concentration of esterified and free cholesterol, did not significantly affect basal plasma level of corticosterone. Morphometry showed a conspicuous hypertrophy of zona fasciculata cells, coupled with a striking proliferation of smooth endoplasmic reticulum (SER) and peroxisomes and with a profound lipid-droplet depletion. The secretory response of zona fasciculata cells to ACTH was still present, but reduced by half with respect to control rats. The simultaneous administration of mevinolin, an inhibitor of cholesterol synthesis, to 4-APP-treated rats caused an additional drop in the intracellular content of free cholesterol and notably lowered basal plasma corticosterone concentration. Mevinolin magnified the 4-APP-induced zona fasciculata cell hypertrophy, as well as SER and peroxisome proliferation. The secretory response to ACTH was completely suppressed. These data are compatible with the view that the morphological changes, which rat zona fasciculata cells undergo during prolonged hypocholesterolaemia, are the expression of the activation of the endogenous cholesterol synthesis. This compensatory response, enabling zona fasciculata cells to maintain a normal basal rate of hormonal output and to respond (though less efficiently) to their main physiological stimulus, seems to be completely independent of any activation of the hypothalamo-hyphophyseal axis, since dexamethasone/ACTH treated rats were used. The hypothesis is advanced that the mechanism underlying this response may involve the decrease of the intracellular free-cholesterol pool.
Adenine↗
Effects of prolonged dopamine infusion on the zona glomerulosa of sodium-restricted rats treated or not with prolactin: stereology and plasma hormone concentrations.
Prolonged sodium restriction was found to induce a notable hypertrophy of rat zona glomerulosa (ZG) cells and a significant rise in the basal plasma aldosterone concentration. Chronic prolactin administration significantly furthered the effects of sodium restriction. Dopamine infusion (3 mg/kg day for 7 days) did not apparently affect ZG morphology and function in the control rats, while it significantly counteracted the effects of sodium deprivation combined or not with prolactin administration. However, the action of dopamine was less intense in sodium-deprived rats treated with prolactin. These findings confirm the view that the dopaminergic system exerts a tonic inhibitory effect, modulated by the sodium balance, on the growth and secretory activity or rat ZG. Moreover, they suggest that the mechanism(s) underlying the antiadrenoglomerulotrophic action of dopamine in rats only partially involve(s) the well-known suppression of the hypophyseal release of prolactin.
Adrenal Cortex↗
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.
Animals↗
Further investigations on the atrial natriuretic factor (ANF)-induced inhibition of the growth and steroidogenic capacity of rat adrenal zona glomerulosa in vivo.
A prolonged infusion with ANF (20 micrograms/kg/h for 7 days) induced atrophy of zona glomerulosa cells and lowering of basal plasma concentration of aldosterone in rats whose hypothalamo-hypophyseal-adrenal axis and renin-angiotensin system had been interrupted by the simultaneous administration of dexamethasone/captopril and maintenance doses of ACTH/angiotensin II. Chronic ANF treatment also caused comparable reductions in the aldosterone response of zona glomerulosa cells to the acute stimulation with angiotensin II, potassium and ACTH. These data are interpreted to indicate that ANF exerts an inhibitory effect on the growth and secretory activity of rat zona glomerulosa, and that the mechanism underlying this action of ANF does not involve blockade of renin release or ACTH secretion.
Adrenal Cortex↗
Long-term stimulatory effect of neuropeptide-Y on the growth and steroidogenic capacity of rat adrenal zona glomerulosa.
A prolonged infusion with neuropeptide-Y (NPY) caused a notable hypertrophy of the adrenal zona glomerulosa and its parenchymal cells in rats whose hypothalamo-hypophyseal axis and renin-angiotensin system were pharmacologically interrupted. Zona glomerulosa hypertrophy was associated with a significant rise in both basal and stimulated plasma levels of aldosterone. Zona fasciculata cells and the blood concentration of corticosterone were not affected. These findings suggest that NPY is specifically involved in the stimulation of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.
Adrenal Cortex↗
Effect of mevinolin on rat hepatocytes: a morphometric study.
A short-term (12 h) infusion with mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, significantly lowered plasma cholesterol concentration in rats. After 7 days of continuous treatment hypocholesterolaemia disappeared, and this was coupled with a notable increase in the average volume of hepatocytes. Liver-cell hypertrophy was associated with a striking proliferation of the membranes of both rough and smooth endoplasmic reticulum, as well as with a tremendous increase in the number of peroxisomes. These structural changes are interpreted as the morphologic counterpart of the compensatory response of rat liver to the prolonged inhibitory effect of mevinolin on cholesterol synthesis.
Animals↗
Long-term trophic effect of sodium restriction on the rat adrenal zona glomerulosa. I. Its partial independence of the renin-angiotensin system.
The mechanism of the trophic effect of chronic sodium restriction on the zona glomerulosa of the rat adrenals was investigated by combined morphometric and biochemical techniques. In the normal rats, prolonged sodium deprivation caused a significant hypertrophy of the zona glomerulosa and its parenchymal cells, coupled with a conspicuous rise in the plasma concentration of aldosterone. Analogous results were observed in animals simultaneously administered captopril and maintenance doses of angiotensin II. However, in this last case, the changes were significantly lower than those observed in the normal rats. These findings are compatible with the view that the activation of the renin-angiotensin system is not the sole mechanism involved in the stimulation of the growth and steroidogenic capacity of rat adrenal zona glomerulosa induced by chronic sodium restriction.
Adrenal Glands↗
Long-term trophic effect of sodium restriction on the rat adrenal zona glomerulosa. II. The possible involvement of the inhibition of the dopaminergic system.
The effects of chronic administration of metoclopramide or bromocriptine (two drugs which act as antagonist and agonist of dopamine receptors) on the zona glomerulosa of captopril-treated rats administered maintenance doses of angiotensin II, were investigated by combined morphometric and biochemical techniques. It was found that metoclopramide provoked a significant hypertrophy of the zona glomerulosa and its parenchymal cells, coupled with a persistent rise in the plasma concentration of aldosterone, only in rats fed a normal diet. Conversely, bromocriptine exerted an evident inhibitory effect on the zona glomerulosa growth and steroidogenic capacity only in chronically sodium-deprived animals. These findings strongly suggest that sodium balance modulates the activity of the dopaminergic system, whose chronic suppression may be involved in the mechanism underlying the extra-angiotensin adrenoglomerulotrophic effect of prolonged sodium restriction.
Adrenal Glands↗
A morphometric study of the effects of melatonin on the rat adrenal zona glomerulosa.
The effects of a long-term administration of melatonin on the zona glomerulosa were investigated both in "normal" rats and in animals in which the hypothalamo-hypophyseal-adrenal axis and the renin-angiotensin system had been pharmacologically interrupted. Melatonin caused a notable hypertrophy of zona glomerulosa cells and a significant rise in the plasma concentration of aldosterone in both groups of rats. These findings indicate that melatonin exerts in vivo a strong direct stimulatory action on the growth and steroidogenic capacity of the rat zona glomerulosa.
Adrenal Glands↗
Zona glomerulosa morphology and function in streptozotocin-induced diabetic rats.
Streptozotocin-induced diabetic rats showed a significant lowering in both PRA (-31%) and basal plasma aldosterone concentration (-59%), coupled with a notable atrophy of the zona glomerulosa (-30%) and its parenchymal cells (-36%). Kalaemia and the blood level of ACTH were not affected. Insulin infusion reversed all the streptozotocin-evoked effects. Analogous, though less conspicuous, changes were induced by experimental diabetes also in rats whose hypothalamo-hypophyseal-adrenal axis and renin-angiotensin system had been pharmacologically interrupted by the simultaneous administration of dexamethasone-captopril and maintenance doses of ACTH-angiotensin II: the drops in the basal plasma aldosterone concentration and in the volume of zona glomerulosa and its cells ranged from -20% to -22%. In these animals, experimental diabetes significantly depressed the aldosterone response to the acute stimulation with angiotensin II (-55%), potassium (-50%), and ACTH (-43%). These findings indicate that the well known impairment of renin release may only partially account for the antiadrenoglomerulotrophic effect of experimental diabetes in rats. The hypothesis is advanced that the chronic lack of insulin may directly depress both the growth of the zona glomerulosa and the newly synthesis of some enzymes of aldosterone synthesis.
Adrenal Glands↗
A morphometric study of the effects of short-term starvation on rat hepatocytes.
Short-term (24 h) starvation induced a significant decrease in the liver weight and in the average volume of hepatocytes, together with a notable decrease in the hepatic concentration of proteins, glycogen, cholesterol and triglycerides. Hepatocyte atrophy was due for about 95% to the decrease in the membrane space, in which glycogen and endoplasmic reticulum membranes are contained, and for about 5% to the depletion of lipid droplets, in which cholesterol and triglycerides are stored. Nuclei, mitochondria and rough endoplasmic reticulum did not display appreciable modifications. The smooth endoplasmic reticulum underwent a net decrease, comparable with the decrease in the liver protein content, and the volume of dense-body compartment was increased, mainly through the rise in the number of microautophagic vacuoles and secondary lysosomes. These last findings were interpreted as the morphological counterpart of the fasting-induced enhancement of protein degradation in rat liver.
Animals↗
Investigations on the possible involvement of the dopaminergic system in the modulation of the growth and steroidogenic capacity of the rat adrenal zona glomerulosa: a coupled morphometric and biochemical study.
The effects of metoclopramide (MTC) and bromocriptine (BRC) (two drugs which act as antagonist and agonist of DOPA-receptors, respectively) on the zona glomerulosa of dexamethasone/ACTH-treated rats were investigated by coupled biochemical and morphometric techniques. Short-term (1-h) MTC administration significantly increased the plasma concentration of aldosterone, while long-term (7-day) MTC administration, as well as short- and long-term treatment with BRC did not cause any apparent change. Long-term MTC administration was found to significantly potentiate both the rise in the plasma level of aldosterone and the hypertrophy of the zona glomerulosa and its parenchymal cells induced by a prolonged treatment with angiotensin II (AII), but not those evoked by a chronic sodium deprivation alone or combined with AII infusion. Long-term BRC administration notably counteracted the effects of sodium restriction (coupled or not with AII infusion), but not those induced by the administration of AII alone. Long-term MTC administration partially reversed both the lowering of the plasma concentration of aldosterone and the atrophy of the zona glomerulosa and its parenchymal cells caused by a prolonged sodium-loading (combined or not with captopril infusion), but not those produced by the administration of captopril alone. On the other hand, long-term BRC treatment induced a further significant reduction in the blood level of aldosterone and the volume of zona glomerulosa and its cells only in captopril-treated animals. These findings are consistent with the view that the dopaminergic system exerts a maximal tonic inhibitory effect not only on the secretory activity, but also on the growth and steroidogenic capacity of the rat zona glomerulosa. Furthermore, they suggest that the activity of the dopaminergic system is in turn controlled by the sodium balance, being almost completely suppressed by a prolonged sodium deprivation.
Adrenal Cortex↗