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Biomedical subjects

A Kasprzak

Publications and source records attributed to A Kasprzak.

At least 37 records · Page 2Linked to original sources

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↗

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↗

The immunobiology of murine interleukin-1 alpha encoded by recombinant vaccinia virus.

Recombinant vaccinia viruses were constructed which encoded murine interleukin-1 alpha (IL-1 alpha) (VV-IL1). One virus also encoded the hemagglutinin (HA) gene of influenza virus (VV-HA-IL1). Mice were infected with these viruses and the effects of co-expressed IL-1 on various immune parameters were assessed. The growth of VV-IL1 in vivo was less than that of the control virus, and this was reflected in the reduced virus-induced cell-mediated immune responses. However, specific antibody responses generated after challenge with vaccinia or influenza viruses were significantly higher when VV-HA-IL1 was used to prime mice, compared to the control virus (VV-HA-TK). This study demonstrates that co-expressed cytokines may be useful for selective alteration of immune reactivity.

Animals↗

Interleukin-1 beta enhances corticosterone secretion by acting directly on the rat adrenal gland.

Interleukin-1 (IL-1), a monokine released by activated monocytes during the acute phase of the inflammatory responses, has been reported to enhance hypophyseal ACTH release mainly by stimulating hypothalamic CRF secretion. We investigated a possible direct effect of IL-1 beta on the adrenal gland of the rat. IL-1 beta was found to dose-dependently (4-8 micrograms/kg) raise corticosterone (B) blood concentration in hypophysectomized rats, without inducing any significant increase in the level of circulating ACTH. IL-1 beta did not affect B production by either isolated rat inner adrenocortical cells or fragments of adrenocortical autotransplants lacking chromaffin cells, but dose-dependently (10(-8)-10(-6) M) enhanced that by adrenal slices including both cortex and medulla. The secretory effect of IL-1 beta (10(-6) M) was completely blocked by both alpha-helical-CRF (10(-6) M) and corticotropin-inhibiting peptide (10(-6) M), two competitive inhibitors which (at these concentrations) were able to annul B response of adrenal slices to CRF (10(-6) M) and ACTH (10(-8) M), respectively. In light of many findings indicating that adrenal medulla contains and releases CRF and numerous POMC-derived peptides (including ACTH), the hypothesis is advanced that the mechanism underlying the direct secretory effect of IL-1 beta on the adrenal gland may involve the activation of an intraadrenal CRF/ACTH system.

Adrenal Glands↗

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↗

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↗

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↗

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↗

Effects of unilateral adrenalectomy on the remaining adrenal cortex of adrenocorticotropic hormone-treated male and female hamsters.

Sham-operated and unilaterally adrenalectomized male and female hamsters were administered 25 micrograms adrenocorticotropic hormone (ACTH) for 5 days after the operation in order to examine the effects of ACTH on compensatory adrenal growth. In ACTH-treated male and female hamsters, unilateral adrenalectomy did not change the relative weight of the remaining adrenal. There were no significant differences in the volumes of the adrenocortical zones and their parenchymal cells, as well as in the number of adrenocortical cells per gland if compared with unilaterally adrenalectomized and sham-operated ACTH-treated male hamsters, while 3H-thymidine incorporation per gland was lower in monoadrenalectomized animals. On the contrary, in ACTH-treated females, unilateral adrenalectomy resulted in a significant hypertrophy of zona fasciculata cells and in an enhanced 3H-thymidine uptake by the remaining gland. These findings stress the existence of notable sex-related differences in the compensatory adrenal growth in hamsters.

Adrenal Cortex↗

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↗

Compensatory adrenal growth in aldosterone-treated male and female hamsters.

The aim of the study was to investigate the compensatory adrenal growth in aldosterone-treated male and female hamsters. Hemiadrenalectomised and sham-operated animals were treated for 5 days with a daily d-aldosterone dose of 25 micrograms/animal. In both male and female aldosterone-treated hamsters monoadrenalectomy did not change the relative adrenal weight if compared with sham-operated groups. The fasciculata zonae of monoadrenalectomised aldosterone-treated males was larger and contained more parenchymal cells than in appropriate control group. There was no difference in the volume of adrenocortical zones, average cell volume and in cell number between sham-operated and unilaterally adrenalectomised females. In vitro 3H-thymidine incorporation per adrenal was markedly higher in monoadrenalectomised than in sham-operated aldosterone-treated males while the opposite was true for female hamsters. Thus, the action of aldosterone on CAG in the hamster seems to depend on sex, with no effect in males and inhibitory action in females.

Adrenal Glands↗

Sex differences in adrenocortical structure and function. XXI. The effects of gonadectomy and testosterone or estradiol replacement on mitotic activity of the rat adrenal cortex.

The study was designed to investigate the mitotic activity of adrenal cortex in the adult male and female rats and to explain the effects of gonadal hormones on proliferation of rat adrenocortical cells. Mitotic index in individual zones of the adrenal cortex as well as a total number of mitoses on the "equatorial" sections of the gland were estimated in dexamethasone and colchicine pretreated control, gonadectomized and gonadectomized-gonadal hormone replaced rats. If compared with males, mitotic index of the zona reticularis (ZR) cells was higher in females, however, there was no difference in the remaining zones of the cortex. Neither orchiectomy nor testosterone had an effect on mitotic index of the zona glomerulosa (ZG) and zona fasciculata (ZF) cells. In the ZR, orchiectomy increased this index, an effect reversed by testosterone. Neither ovariectomy nor estradiol administration had an effect on mitotic index of the ZG and ZF, while in the ZR estradiol lowered this index if compared with control and gonadectomized rats. Total number of mitoses per "equatorial" section of the gland was similar in male and female rats. Orchiectomy increased this value, an effect reversed by testosterone. On the other hand, neither ovariectomy nor estradiol had an effect on the total number of mitoses per section of the adrenal gland.

Adrenal Cortex↗

Short- and long-term effects of angiotensin II on the rat adrenal zona glomerulosa. A coupled stereological and enzymological study.

Long-term angiotensin II administration induced a time-dependent increase in the volume of rat zona glomerulosa cells and in the plasma concentration of aldosterone. Cell hypertrophy is coupled with comparable increases in the surface area per cell of mitochondrial cristae and in the activity per cell of 18-hydroxylase. 11 beta-hydroxylase activity was not affected. These findings allow to suggest that the angiotensin-II-enhanced growth of rat zona glomerulosa is associated with the de novo synthesis of 18-hydroxylase.

Adrenal Cortex↗

Comparative stereological studies on the effects of long term CRF and ACTH treatment on the cortex of the suprarenal gland.

The aim of the study was to investigate by means of stereological and biochemical methods the effects of long-term CRF administration on the cortex of the suprarenal gland of adult male rats and to compare these effects with those of ACTH. Both CRF (administered into the lateral ventricle of the brain) and ACTH resulted after 8 days in an increase in weight of the suprarenal gland. Both treatments increased the volume of individual adrenocortical zones and the average volume of adrenocortical cells as well as enhancing the total number of parenchymal cells in the paired glands. There was also no significant difference in those functional parameters studied of the adrenocortical cells of CRF- and ACTH-treated rats. Thus, long term treatment of adult male rats with CRF evoked adrenocortical changes similar to those observed after ACTH administration.

Adrenal Cortex↗

Sex differences in adrenocortical structure and function. XIX. Differences in the compensatory hypertrophy of the adrenal cortex of the male and female hamster after unilateral adrenalectomy.

Stereological studies on the adrenal cortex of unilaterally adrenalectomised hamsters have revealed differences in adrenal compensatory hypertrophy in male and female animals. The operation evokes an increase in the average volume of the zona fasciculata cells in the male and of the zona reticularis cells in the female.

Adrenal Cortex↗

Sex differences in adrenocortical structure and function. XIII. Stereologic studies on adrenal cortex of maturing male and female hamsters.

Adrenal glands of adult male hamsters are larger and secrete more cortisol than those of females. Stereology was therefore used to study zonal and cellular aspects of development of the adrenal cortex of male and female hamsters. Adrenal glands were studied at weekly intervals from day 21 to day 77 of postnatal ontogenesis. Within this period, body weight did not differ significantly between the sexes. During development, absolute and relative adrenal weights were higher in males; their zona glomerulosa (ZG), zona fasciculata (ZF) and zona reticularis (ZR) become markedly larger than those in females. No marked changes in the volume of individual ZG cells occurred although ZF cells and ZR cells become larger in male than female animals. The total number of adrenocortical cells increased within the period studied, a greater increase being observed in ZG and ZF in males. No distinct sex difference was observed in the number of ZR cells throughout development. From day 56 of postnatal life the adrenal cortex of male hamster contained more parenchymal cells than the female gland. These results thus indicate that sex differences in hamster adrenal cortex depend upon changes in number and size of parenchymal cells.

Adrenal Cortex↗