Biomedical subjects

L K Malendowicz

Publications and source records attributed to L K Malendowicz.

At least 145 records · Page 8Linked to original sources

PubMed1992

Neurotensin enhances plasma adrenocorticotropin concentration by stimulating corticotropin-releasing hormone secretion.

The systemic administration of neurotensin (NT) dose-dependently increased plasma adrenocorticotropin (ACTH) concentration in rats, and this effect was annulled by (alpha-helical)-CRH9-41, an antagonist of corticotropin-releasing hormone (CRH). The systemic administration of [D-Trp11]-neurotensin (NT-A), a specific NT antagonist, dose-dependently reduced the basal level of circulating ACTH, and this effect was blunted by NT injection. The ACTH inhibitory action of NT-A was completely overcome by the administration of CRH. Taken together, our findings suggest that NT plays a physiologic role in rats, as ACTH secretagogue, and that the mechanism underlying this action of NT involves the stimulation of CRH release.

Adrenocorticotropic Hormone↗

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

Comparison of the effects of neurotensin and vasopressin on the adrenal cortex of dexamethasone-suppressed rats.

Neurotensin (NT) and vasopressin (AVP) share some similarities as far as their actions on the adrenal weight and secretion are concerned. The present study aimed to compare the in vivo chronic effect of these two peptides on the adrenal cortex of dexamethasone (Dx)-treated rats. NT or AVP were ip. infused at a rate of 2 micrograms/rat/d for 7 d. In the animals concomitantly treated with 15 micrograms Dx/100 g/d for 7 d, both NT and AVP partially prevented adrenal atrophy. AVP enhanced plasma aldosterone concentration (PAC), but not that of corticosterone (PBC). On the other hand, NT did not affect either PAC or PBC. In rats treated with 35 micrograms Dx/100 g/d for 14 d, neither NT nor AVP administered for the last 7 d exerted any effect on the adrenal weight. However, also under these conditions of profound adrenal atrophy AVP was still able to notably raise PAC, while NT was ineffective. Our findings indicate that the mechanism underlying the aldosterone secretagogue action of AVP does not require, unlike that of NT, the presence of ACTH. Moreover, in light of many recent literature data they could suggest the possibility that in vivo NT acts on the rat adrenal cortex via AVP.

Adrenal Cortex↗

PubMed1992

Calcitonin gene-related peptide depresses the growth and secretory activity of rat adrenal zona glomerulosa.

The bolus ip. injection of rat calcitonin gene-related peptide (CGRP) (5 pm. kg-1) significantly lowered plasma aldosterone concentration (PAC) in rats, despite a mild rise in plasma renin activity. Natremia, kalaemia and the blood levels of ACTH or corticosterone were not affected. Similar results were obtained after prolonged (5 days) sc. infusion of rats with CGRP (1 pm. kg-1. h-1). Moreover, CGRP infusion caused a notable atrophy of the zona glomerulosa (ZG) and its parenchymal cells, as well as a clearcut reduction in the surge of PAC evoked by a bolus injection of a high dose of angiotensin-II (100 micrograms. kg-1). From these results it is suggested that CGRP exerts an inhibitory effect on the growth and secretory activity of ZG in rats.

Adrenocorticotropic Hormone↗

PubMed1992

Comparative studies on the effect of 4-APP(4-aminopyrazolopyrimidine) on hamster and rat adrenal cortex.

The study aimed to compare, by means of stereologic methods, the reactivity of the adrenal cortex of the hamster and the rat to prolonged treatment with 4-aminopyrazolo-(3,4d)pyrimidine (4-APP), a drug reducing hepatic secretion of plasma lipoprotein. Adult female hamsters, intact or cortisone suppressed, were administered i.p. daily with 0.5 mg 4-APP for 5 days while intact female rats received 1 mg of the drug per dose. 4-APP resulted in a loss of body weight, with the more profound effect in the hamster. In the rat 4-APP did not change the adrenal gland weight, the volume of the adrenocortical zones, the average volume of adrenocortical cells and the number of parenchymal cells in the gland. Moreover, serum ACTH and corticosterone levels in the rat remained unchanged. In the intact hamster 4-APP decreased the adrenal gland weight, the volume of the zona fasciculata and enhanced the serum cortisol level. In steroid suppressed hamsters 4-APP lowered the adrenal weight, the volume of fasciculata and reticularis zones, the average volume of the fasciculata cells and the number of parenchymal cells in the gland. These findings may suggest the direct inhibitory effect of low 4-APP doses on the hamster adrenal cortex and clearly demonstrate higher susceptibility of the hamster adrenal cortex, if compared with the rat, to 4-aminopyrazolo-pyrimidine.

Adenine↗

PubMed1992

Comparative studies on the effects of aminoglutethimide on hamster and rat adrenal cortex.

Adult female, intact or steroid suppressed hamsters were treated twice daily with 7 mg aminoglutethimide phosphate (AG) for 5 days while intact female rats received 14 mg AG per injection. AG resulted in an increase in adrenal gland weight of both hamster and rat. In the hamster AG had no effect on the amount of lipid droplets while in the rat a slightly higher number of fine lipid vacuoles was seen. In the hamster, enlargement of the gland was due to hyperplasia of the zona reticularis cells while in the rat the number of glomerulosa and fasciculata cells increased. AG had no effect on the adrenal cortex of steroid suppressed hamsters. The serum cortisol level was markedly higher in AG-treated hamsters while the corticosterone level was notably lower in AG-administered rats. In both hamsters and rats, AG-treatment did not change the serum ACTH level. Thus the study demonstrated different responses of the hamster and rat adrenal cortex to AG.

Adrenal Cortex↗

PubMed1992

Dexamethasone-induced adrenal cortex atrophy and recovery of the gland from partial, steroid-induced atrophy.

This study aims to examine the effects of low dexamethasone (DX) doses on cellular and functional changes in the rat adrenal cortex and to observe the recovery of the gland from DX-induced partial atrophy. Within seven days doses of 15, 30 and 60 micrograms DX/100 g/day resulted in a dose dependent decrease in body and adrenal gland weight. Within two weeks the lowest DX dose tested caused further decrease in adrenal weight. DX markedly lowered plasma ACTH and corticosterone (B) level, B content in the gland and B output by adrenal slices. Adrenocortical atrophy induced by 15 micrograms DX was dependent upon the linear decrease in the volume of fasciculata and reticularis zones, in the average volume of the fasciculata cell and in the number of adrenocortical cells in the entire cortex. This dose of DX resulted in a prompt and potent inhibition of proliferative activity of adrenocortical cells as assessed by the counting of metaphases per adrenal section. Partial adrenal atrophy evoked by 7 day DX-treatment was reversible within seven days of the discontinuation of the steroid treatment. Recovery of the gland depended mainly on the increases in the volume of all adrenocortical zones, in the average volume of fasciculata cell and in the number of parenchymal cells in the gland. Seven days after discontinuation of DX administration plasma ACTH was significantly higher than in controls. Plasma B and B secretion by adrenal slices were similar to the control group while B content in the gland was still depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

PubMed1992

Sex differences in adrenocortical structure and function: 29. Morphometric and functional studies on the effects of gonadectomy and gonadal-hormone replacement on the hamster adrenal cortex.

The morphologic changes evoked in the adrenal glands of male and female hamsters by gonadectomy (15 weeks) and gonadal-hormone replacement (single s.c. injection of 5 mg/100 g b.w. testosterone or 0.5 mg/100 g b.w. estradiol, 2 weeks before the sacrifice) were investigated by morphometric techniques and correlated with the functional alterations of the hypothalamopituitary-adrenal axis. Our findings evidenced a stimulatory role of androgens and a moderate inhibitory one of estrogens on the growth and steroidogenic capacity of the adrenal glands in male and female hamsters, respectively. Moreover, they suggest that these adrenal effects of gonadal hormones are, at least partly, independent of alterations in the pituitary ACTH release.

Adrenal Cortex↗

PubMed1992

ACTH-induced ultrastructural changes in the zona fasciculata of the hamster adrenal cortex. Are intraadrenal thrombi regulators of corticosteroid secretion?

Correlated stereological and functional studies were performed on the effect of massive ACTH doses on adrenal cortex of the female hamster. ACTH resulted in a marked increase in adrenal gland weight at day 6 of treatment followed by a drop at day 9. Stereology showed significant enlargement of the zona fasciculata (ZF) cells with the highest value at day 6 and subsequent drop at day 9 of treatment. This hypertrophy was due to a notable increase in the volume of mitochondrial, SER, Golgi apparatus and lipid droplet compartments. Cortisol secretion by adrenal slices and homogenates was also highest at day 6 of ACTH administration and notably lower at day 9. At day 6 of ACTH treatment in outer ZF thrombi were seen. In their vicinity the subendothelial space was dilated and endothelial cells dissociated from the basal lamina. Numerous erythrocytes were also visible among dissociated ZF cells. At day 9 of experiment in outer part of ZF numerous spaces devoid of parenchymal cells appeared. The earlier authors considered the "empty spaces" or "holes" in hyperstimulated adrenal cortex as a sign of holocrine secretion of steroid hormones. The present findings enable us to introduce a new hypothesis on the development of these spaces. In our opinion in hyperstimulated adrenal cortex numerous thrombi may be formed leading thus to the degeneration of adrenocortical cells. Thus, the appearance of the "empty spaces" or "holes" in the gland is not connected with the holocrine secretion but with the regulation of the number of secretory cells in adrenal cortex by the thrombi-dependent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1992

Endothelin-1 stimulates mitotic activity in the zona glomerulosa of the rat adrenal cortex.

Subcutaneous infusion with endothelin-1 (ET-1; 30 pM min-1) for 24 h induced a 9-fold increase in the mitotic index (% of metaphase-arrested cells) of rat adrenal zona glomerulosa (ZG). Infusions with adrenocorticotrophic hormone (ACTH) angiotensin-II (ANG-II) or arginine vasopressin (AVP) (30 pM min-1/24 h) raised the ZG mitotic index 13-fold, 9-fold and 10-fold, respectively. Combined infusion with ET-1 and ACTH increased the ZG mitotic index 20-fold, while the effects of ET-1 and ANG-II or AVP were not additive. These findings suggest that ET-1 exerts a strong proliferogenic effect on the rat ZG, by a mechanism probably similar to that underlying the adrenoglomerulotrophic actions of ANG-II and AVP.

Adrenocorticotropic Hormone↗

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↗

PubMed1992

Analysis of the preventive action of ACTH on dexamethasone-induced adrenocortical atrophy in the rat.

Adult female rats were treated for 4 or 6 days consecutively with dexamethasone (Dx; 100 micrograms kg-1 day-1) alone or with ACTH (100 micrograms kg-1 day-1) for 2, 4 or 6 days. After 2 days of ACTH administration, zona fasciculata cells increased in volume, and the blood concentration of corticosterone was raised. Basal corticosterone secretion by adrenal slices appeared to be enhanced by ACTH treatment only when calculating per adrenal pair (and not per unit wt of adrenals). A significant increase in the number of metaphase cells was observed after only 4 days of ACTH administration. It is suggested that (1) the first action of ACTH on Dx-suppressed rats is to induce the hypertrophy of adrenocortical cells; (2) the steroidogenic capacity of adrenocortical cells is directly proportional to their average volume; and (3) the stimulatory effect of ACTH on the proliferative activity of adrenocortical cells is subsequent to the stimulation of their specialized functions.

Adrenal Cortex↗

PubMed1992

Morphometric studies on the development of human thyroid gland in early fetal life.

Histological and morphometric studies were performed on 30 thyroid glands obtained from normal human fetuses. Their crown-rump length (CRL) ranged from 57 to 190 mm, corresponding to the gestational age of 10-20 weeks. The weight of the thyroid gland increased proportionally in relation to CRL, foot length and fetus weight. The first follicles containing PAS-positive colloid were observed in the peripheral part of the thyroid gland of 57 mm CRL fetus. The number of follicles per 1 mm2 of thyroid surface section increased up to 85 mm CRL and thereafter gradually declined for the end of studied period of fetal life. The volumes (in mm3) of thyroid epithelium, colloid and stroma, beginning from 85 mm increased proportionally to the CRL while the height of epithelial cells did not change. The epithelium/colloid ratio decreased notably to 165 mm CRL and thereafter remained constant. Results of the present study suggest that the thyroid gland of human fetus approaches structural maturity in 17.5 week of gestation.

Embryonic and Fetal Development↗

PubMed1991

Effect of bombesin on the structure and function of the rat adrenal cortex.

Intact and dexamethasone-treated adult female Wistar rats were infused (Alzet osmotic minipumps) with bombesin (0.75 micrograms/rat per day) for 7 days. Bombesin depressed body weight and capacity of adrenal homogenate to secrete corticosterone; the latter effect was reflected in intact rats by a drop in serum corticosterone level. Bombesin had no effect on pituitary and serum adrenocorticotropic hormone (ACTH) concentration and serum aldosterone level. In intact animals, infusion of bombesin resulted in lowering of the number of parenchymal cells in adrenal cortex connected with the hypertrophy of glomerulosa and fasciculata cells. Moreover, bombesin lowered basal corticosterone secretion by isolated rat adrenocortical cells; however, neuropeptide applied did not change the response of isolated cells to ACTH stimulation. The data obtained clearly demonstrate inhibitory effect of bombesin on basal corticosterone secretion by the rat adrenal cortex.

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

Acute action of polypeptide YY (PYY) on rat adrenocortical cells: in vivo versus in vitro effects.

Polypeptide YY (PYY), a 36-amino-acid peptide contained in high concentration in the chromaffin granules of adrenal medullary cells, significantly raised aldosterone (but not corticosterone) plasma level, when acutely administered intraperitoneum to rats at a dose of 25 microM.kg-1. Conversely, the exposure to PYY (10(-6) M) notably and specifically depressed both basal and ACTH-stimulated production of 18-hydroxylated steroids (aldosterone, 18-hydroxy-corticosterone and 180H-DOC) by isolated rat zona glomerulosa cells. The discrepancy between in vivo and in vitro results is tentatively explained by assuming that the direct inhibitory effect of PYY on aldosterone secretion by rat zona glomerulosa is masked in vivo by the interference of this peptide with one or more of the various factors that are involved in the multifactorial regulation of zona glomerulosa function.

18-Hydroxycorticosterone↗

PubMed1991

Comparison of the effects of neurotensin and ACTH on the pituitary-adrenocortical axis of dexamethasone-suppressed rats.

Neurotensin (NT) (12-48 micrograms/kg-1/day-1, for 2 days, s.c.), like ACTH (60 micrograms/kg-1/day-1, for 2 days, s.c.), counteracted the dexamethasone (Dx)-induced (120 micrograms/kg-1/day-1, for 4 days, s.c.) adrenal zona-fasciculata cell atrophy. NT notably raised, in Dx-suppressed rats, the plasma concentration of ACTH, which reached about that found after exogenous ACTH administration. However, at variance with ACTH, NT did not enhance either plasma corticosterone (B) level or B production by adrenal quarters in vitro. The conclusion is drawn that NT modulates the function of the rat pituitary-adrenocortical axis, by simultaneously stimulating hypophyseal ACTH release and inhibiting steroidogenesis at the adrenal level.

Adrenocorticotropic Hormone↗

PubMed1991

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

Weekly infusion with arginine vasopressin (AVP) (2 micrograms.kg-1.day-1) exerted a slight stimulatory effect on the adrenal growth of intact female rats and induced a 2-fold rise in plasma aldosterone concentration (PAC), without apparently affecting corticosterone (B) and ACTH secretions. Weekly dexamethasone (Dx) administration (125 micrograms.kg-1.day-1) caused a marked adrenal atrophy, a conspicuous suppression of B and ACTH productions, and a 5-fold increase in PAC. AVP infusion reversed the Dx-induced adrenal atrophy. It did not counteract the suppression of B and ACTH secretions, nor did it change PAC. These findings suggest that chronic AVP treatment is able to stimulate adrenal growth by a Dx-insensitive mechanism (i.e. independent of any change in ACTH secretion). Conversely, AVP may enhance the steroid secretory capacity only in adrenocortical cells in which the maintenance of the steroidogenic machinery is assured by normal levels of circulating ACTH.

Adrenocorticotropic Hormone↗