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Biomedical subjects

L K Malendowicz

Publications and source records attributed to L K Malendowicz.

At least 163 records · Page 9Linked to original sources
PubMed1991

Effects of neurotensin on the pituitary-adrenocortical axis of intact and dexamethasone-suppressed rats.

A 7-day infusion with neurotensin (NT) (10 micrograms.kg-1.day-1) stimulated adrenal growth in intact female rats, and raised ACTH blood concentration, without altering corticosterone (B) plasma level and output by adrenal homogenates. For a week dexamethasone (Dx) administration (125 micrograms.kg-1.day-1) caused a notable adrenal atrophy, a marked lowering of ACTH and B blood concentrations, and a profound depression of B output by adrenal homogenates. NT infusion reversed Dx-induced adrenal atrophy and plasma ACTH-level drop, but not the impairment in adrenal-cortex secretory activity. In vitro studies showed that NT (10(-6) mol/l) significantly reduced basal, but not ACTH-stimulated B release by isolated rat inner adrenocortical cells. These findings suggest that NT exerts a direct inhibitory effect on B production by rat adrenals, while it is able to enhance ACTH secretion and consequently adrenal growth. Moreover, they indicate that NT evokes a striking, and at present unexplained dissociation between structure and function in the adrenal cortex of Dx-suppressed rats.

Adrenocorticotropic Hormone↗
PubMed1991

Neurotensin inhibits the stimulatory effect of angiotensin-II and potassium on aldosterone secretion by rat zona glomerulosa cells.

Neurotensin (NT), a hypothalamic peptide which is also contained in the chromaffin granules of adrenal medullary cells, did not affect either basal or ACTH-stimulated secretory activity of isolated rat zona glomerulosa (ZG) cells. Conversely, NT was found to exert a strong dose-dependent inhibitory effect on aldosterone response of ZG cells to their two main calcium-dependent secretagogues angiotensin-II and potassium. These findings suggest that NT may interfere with the angiotensin-II- or potassium-induced activation of protein kinase C, possibly by blunting the rise in the cytosolic calcium concentration.

Adrenocorticotropic Hormone↗
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

Ovariectomy-induced changes in the adrenal cortex of spontaneously hypertensive rats.

Many lines of evidence indicate that adrenocortical steroid hormones are involved in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). Twenty-eight days after ovariectomy a notable decrease in the sistolic blood pressure (BP) was found in SHR, along with a marked atrophy of their adrenal cortices. The hypothesis is advanced that the ovariectomy-induced lowering in BP in SHR may be, at least partly, mediated by the suppression of the adrenal secretory activity, due to the lack of circulating estrogens, which are well known to stimulate hypophyseal ACTH release.

Adrenal Cortex↗
PubMed1990

Effects of prolonged cyclosporine-A treatment on the Leydig cells of the rat testis.

The effects of a prolonged (30-day) treatment with daily therapeutical doses of cyclosporin A (CAS) (20 mg/kg) on testicular Leydig cells were studied in adult rats. CSA administration provoked a significant decrease in both basal and human chorionic gonadotropin (hCG)-stimulated testosterone concentration in the peripheral blood without affecting the volume of the testes or the interstitial space. However, there was conspicuous atrophy of the Leydig cells, due mainly to a decrease in mitochondria and smooth endoplasmic reticulum, the organelles containing the enzymes of testosterone synthesis. Lipid droplets, in which cholesterol is stored, were notably increased. The nuclear volume and the surface area per cell of rough endoplasmic reticulum fell significantly in Leydig cells of CAS-treated animals. In light of these findings, it is concluded that CSA inhibits the growth and steroidogenic capacity of rat Leydig cells, probably by depressing their protein synthesis. Whether the mechanism underlying the action of CSA on Leydig cells is only indirect, by blockade of hypophyseal gonadotropin release, or also direct is unsettled and requires further investigation.

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

Sex differences in adrenocortical structure and function. XXVII. The effect of ether stress on ACTH and corticosterone in intact, gonadectomized, and testosterone- or estradiol-replaced rats.

Studies were performed on the reactivity of the hypothalamo-pituitary-adrenocortical axis of intact, gonadectomized, and testosterone- or estradiol-replaced rats to standard ether stress. Plasma ACTH and corticosterone (B) levels, anterior pituitary ACTH, and adrenal B content were estimated 20 and 40 min after stress application and in unstressed animals. Ether stress resulted in an increase in plasma ACTH and B levels and in adrenal B content while pituitary ACTH content was notably lower when compared with unstressed rats. The response was markedly higher in female than in male rats. After orchiectomy and testosterone replacement, plasma ACTH and B responses to ether stress were similar to those observed in intact male rats. On the other hand, ovariectomized females responded to ether stress like intact males, while after estradiol replacement the pattern of plasma ACTH and B concentration and adrenal B content was similar to that in intact female rats. Thus, the higher responsiveness of the pituitary-adrenal cortex axis of female rats to ether stress depends on stimulatory or facilitatory effect of estradiol.

Adrenal Glands↗
PubMed1990

Gestational changes in hamster adrenal cortex: stereologic and functional studies.

Pregnancy in hamsters evoked a prompt increase in adrenal weight, with the highest value at day 5 and a subsequent fall toward the end of gestation. The surface densities of mitochondrial cristae and smooth endoplasmic reticulum did not display significant changes in the course of gestation, while 11 beta-hydroxylase and 3 beta-hydroxysteroid dehydrogenase/isomerase activity (two enzymes located in these two organelles) underwent significant increases at day 5 and day 10 of pregnancy, respectively. Neither the adrenal content of cortisol nor cortisol output by adrenal homogenates changed, but cortisol production measured in adrenal slices gradually rose during the course of pregnancy. Blood cortisol concentration increased about ten-fold toward the end of gestation, whereas the plasma ACTH level remained unchanged and plasma aldosterone concentration was significantly lowered. The conclusion is drawn that the pregnant hamster's adrenal glands possess an enhanced capacity to secrete cortisol, but the factor(s) involved remain unknown.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Sex-dependent effect of melatonin on the secretory activity of rat and hamster adrenal gland in vitro.

Adrenal quarters from adult male or female hamsters were incubated in the presence of melatonin (10(-7) or 10(-4)M), and cortisol concentration in the incubation medium was assayed by RIA. Melatonin did not change cortisol output by adrenals obtained from the male hamsters, while a slight stimulatory effect was observed in female glands, the lower concentration of melatonin being more effective than the higher one. At both concentrations tested, melatonin notably stimulated corticosterone output by isolated rat adrenocortical cells derived from the males, and lowered corticosterone secretion by the cells obtained from the female glands only at a concentration of 10(-7) M. The lower concentration of melatonin increased ACTH (0.1 mU.ml-1)-stimulated corticosterone output by the cells of male and female rat adrenals. The pineal hormone was ineffective at a concentration of 10(-4) M, as well as in the presence of a higher dose of ACTH (1.0 mU.ml-1). These findings indicate a distinct sex-dependent effect of melatonin on in vitro cortisol and corticosterone production, and demonstrate that the modulatory effect of melatonin of the secretion of steroid hormones is more effective at lower concentrations.

Adrenal Glands↗
PubMed1990

Long-term effects of neuropeptide-Y on the rat adrenal cortex.

Adult female rats, intact or dexamethasone suppressed, were i.p. injected twice a day for 4 consecutive days with 0.5 ug neuropeptide-Y (NPY). In intact rats, NPY lowered serum ACTH and aldosterone levels, and had no effects either on serum and adrenal corticosterone or the morphology of the adrenal cortex. In dexamethasone-treated rats, NPY again decreased serum aldosterone concentration. Moreover, it caused a small but significant drop both in the volume of zona fasciculata cells and the adrenal content of corticosterone. These findings seem to suggest an inhibitory effect of NPY on the function of rat zona glomerulosa and perhaps zona fasciculata.

Adrenal Cortex↗
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

Proliferation and distribution of adrenocortical cells in ACTH treated female hamsters.

The aim of the study was the analysis, by means of combined stereologic methods and metaphase arrest technique of the adrenocortical growth of ACTH treated hamster. Adult female hamsters were treated daily with 50 micrograms ACTH (Synacthen Depot, Ciba) for 3, 6 and 9 days. Between days 3 and 9 nearly linear increase in adrenal gland weight was observed, mainly due to the enlargement of the fasciculata and reticularis zones. Throughout the experiment, there was no marked change in the number of the zona glomerulosa cells while from the day 3 a notable increase in the number of fasciculata and reticularis cells occurred. Prolonged ACTH treatment resulted in a significant increase in 3H-thymidine incorporation with the highest value on day 6 and subsequent drop on day 9. Also metaphase index of adrenocortical cells notably increased due to ACTH administration and again the highest value was found on day 6 of experiment. From stereologic data and from metaphase index, adrenocortical cell birth-rates in individual adrenocortical zones and in the entire cortex were calculated. There were great differences between the values calculated from metaphase index and those obtained from stereologic data, with the former significantly lower. ACTH enhances centripetal migration of parenchymal cells in the hamster adrenal cortex and causes their accumulation in the zona reticularis.

Adrenal Cortex↗
PubMed1990

Proliferation and distribution of adrenocortical cells in the gland of ACTH- or dexamethasone-treated rats.

The effects of prolonged (7-day) ACTH and dexamethasone administrations on rat adrenocortical-cell turnover have been investigated by combined stereological and metaphase-arrest techniques. ACTH was found to increase the number of parenchymal cells in each adrenal zone; however, ACTH altered the cell distribution in the cortex, lowering their percentage in the zona glomerulosa (ZG) and zona fasciculata (ZF) and enhancing it in the zona reticularis (ZR). The cell birth-rate was markedly raised by ACTH exclusively in ZG and ZF. Dexamethasone notably decreased the number of ZF and ZR cells, without altering that of ZG cells. Moreover, dexamethasone increased the percentage of parenchymal cells in ZG and ZF, and lowered it in ZR. In the adrenal cortices of dexamethasone-administered animals, metaphases were virtually absent. These data indicate that ACTH increases the cell birthrate in ZG and possibly ZF, and enhances the centripetal migration of newly-formed cells and their accumulation in ZR. Dexamethasone inhibits both proliferation of adrenocortical cells in the outer cortical layers and their centripetal migration into ZR. Moreover, it appears to cause parenchymal-cell loss in the inner adrenocortical layers.

Adrenal Cortex↗
PubMed1990

Sex differences in adrenocortical structure and function. XXVIII. ACTH and corticosterone in intact, gonadectomised and gonadal hormone replaced rats.

Plasma ACTH and corticosterone (B) concentration, ACTH content in the anterior pituitary gland and B content in the adrenals were measured in intact, gonadectomised and testosterone or estradiol replaced rats. Plasma ACTH and B levels and adrenal B content were higher in female than male rats. Neither orchiectomy nor testosterone replacement had an effect on plasma ACTH and B concentration. Orchiectomy did not affect adrenal B content and decreased pituitary ACTH while testosterone significantly lowered ACTH and B content in studied glands. On the other hand ovariectomy did not change pituitary ACTH and adrenal B content and notably lowered concentrations of these hormones in the blood. Estradiol replacement resulted in an increase in plasma ACTH and B concentrations, an effect accompanied by a marked drop in pituitary ACTH and an increase in adrenal B. These findings indicate the distinct sex differences in basal plasma ACTH and B concentrations with higher values in female rats, an effect dependent on the stimulatory action of estradiol on pituitary-adrenocortical axis.

Adrenal Cortex↗
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

Studies on the compensatory growth of the adrenal cortex of the male hamster after unilateral adrenalectomy.

The aim of the study was to investigate the cellular aspects of compensatory growth of the adrenal cortex of male hamster after unilateral adrenalectomy. Relative right adrenal gland weight was higher at 24 h after hemiadrenalectomy with no differences--if compared with sham operated hamsters--at 12, 48, 96 and 120 h. In vitro 3H-thymidine incorporation per mg of adrenal after 12 h was higher and 120 h lower in monoadrenalectomised male hamsters than in sham operated animals with no differences in the remaining time-points studied. If 3H-thymidine incorporation was expressed per entire gland, only 120 h after surgery the uptake was lower than in sham operated animals. Five days after hemiadrenalectomy an increase in the average volume of the zona fasciculata cell and no change in the glomerulosa and reticularis zones were observed. At that day solitary adrenal cortex contained similar number of parenchymal cells as the right adrenal gland of sham operated animals. Thus, hemiadrenalectomy in the male hamster leads to a prompt proliferative response of the contralateral gland at 12 h after surgery, followed by decreased proliferative activity at 120 h after surgery. Monoadrenalectomy increased average volume of the zona fasciculata cell and did not change the total number of parenchymal cells in the gland if compared with sham operated animals.

Adrenal Cortex↗