Biomedical subjects

L K Malendowicz

Publications and source records attributed to L K Malendowicz.

At least 127 records · Page 7Linked to original sources

PubMed1994

Effects of neuromedin U (NMU)-8 on the rat hypothalamo-pituitary-adrenal axis. Evidence of a direct effect of NMU-8 on the adrenal gland.

A 6-day subcutaneous (s.c.) treatment of adult rats with NMU-8 (1.5 or 6 micrograms/100 g/day) increased the average volume of zona fasciculata cells and decreased the number of zona reticularis cells in the adrenal cortex. The lower dose of NMU-8 did not change blood ACTH concentration and adrenal weight, but it notably enhanced serum corticosterone level and basal corticosterone output by adrenal slices. ACTH blood level increased after ether stress in both control and NMU-8-treated rats, but stress-evoked rise in serum corticosterone was observed only in control rats. The higher dose of NMU-8 increased the level of circulating ACTH; however, it decreased adrenal weight and had no effect on serum corticosterone concentration and basal corticosterone output by adrenal slices. NMU-8 (10(-10)/10(-6) M) did not affect basal and ACTH-stimulated corticosterone yield by isolated adrenocortical cells, nor did it change their cytosolic Ca2+ concentration. NMU-8 (10(-8) M) markedly raised basal corticosterone secretion by adrenal slices (including cortex and medulla); higher concentrations of NMU-8 (10(-7)/10(-6) M) were ineffective on basal corticosterone secretion, but strongly inhibited the response to ACTH stimulation. On the ground of these findings it seems reasonable to suggest that NMU-8 exerts a biphasic effect on the function of the peripheral branch of the hypothalamo-pituitary-adrenal axis in rats: NMU-8 at low doses directly stimulates the function and growth of the adrenal cortex, while at high doses exerts a direct inhibitory action.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1994

Evidence that endogenous vasoactive intestinal peptide (VIP) is involved in the regulation of rat pituitary-adrenocortical function: in vivo studies with a VIP antagonist.

The effect of a subcutaneous bolus injection of 2 micrograms magnitude of Ac,Tyr1,D-Phe2-GRF(1-29) amide, a specific VIP antagonist (VIP-A), on the hypothalamo-pituitary-adrenocortical (HPA) axis were investigated in both normal and ether- or cold-stressed rats. Blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA 1, 2 or 4 h after VIP-A injection. VIP-A administration to normal rats strikingly lowered the plasma concentration of ALDO, without significantly affecting those of ACTH and B. Ether and cold stresses notably raised the blood levels of ACTH, ALDO and B, and these rises lasted unchanged until 4 h. VIP-A did not affect the response of HPA axis to ether stress, but provoked a marked depression of that to cold stress. In light of these findings the following conclusions can be drawn: (i) endogenous VIP does not regulate HPA-axis function under basal conditions, but it plays a pivotal role in the mechanisms involved in the activation of HPA axis induced by cold exposure; and (ii) endogenous VIP exerts a tonic stimulatory action on ALDO secretion, probably by acting directly on the adrenal zona glomerulosa.

Adrenal Cortex↗

PubMed1994

Stimulatory effect of vasoactive intestinal peptide (VIP) on the secretory activity of dispersed rat adrenocortical cells. Evidence for the interaction of VIP with ACTH receptors.

VIP dose-dependently increased basal, but not submaximally ACTH (10(-10) M)-stimulated, aldosterone (ALDO) and corticosterone (B) secretion of dispersed rat capsular and inner adrenocortical cells, respectively. The maximal stimulatory effect (60-70% rise) was obtained with a VIP concentration of 10(-8) M. [4-Cl-D-Phe6,Leu17]-VIP, a VIP-receptor antagonist (VIP-A), and corticotropin-inhibiting peptide (CIP), an ACTH receptor antagonist (both 10(-6) M), completely annulled VIP (10(-8) M)-evoked rises in basal ALDO and corticosterone secretions. The ACTH (10(-10) M)-enhanced (about 5-fold) production of both hormones was completely reversed by CIP (10(-6) M) and only partially reduced (about -30%) by VIP-A (10(-6) M). The hypothesis is advanced that the weak secretagogue effect of VIP on dispersed rat capsular and inner adrenocortical cells may be due to its positive interaction with ACTH receptors.

Adrenal Cortex↗

PubMed1994

Effects of cyclosporine-A on steroid secretion of dispersed rat adrenocortical cells.

The acute effect of cyclosporine-A (CSA), a potent immunosuppressive agent, on the secretory activity of dispersed rat adrenocortical cells was investigated. The production of the following steroid hormones was assayed by high performance liquid chromatography: pregnenolone (PREG), progesterone (PROG), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO); B and ALDO outputs were also measured by radioimmunoassay. Low concentrations of CSA (0.1-0.2 mg/ml) enhanced basal, but not ACTH- or angiotensin-II (ANG-II) 10(-8) M-stimulated, secretions of PREG, non-18-hydroxylated steroids (PROG, DOC and B) and 18-hydroxylated steroids (18OH-DOC, 18OH-B and ALDO) of both zona glomerulosa (ZG) and zonae fasciculata and reticularis (ZF/ZR) cells. Middle concentrations of CSA (from 0.3 to 0.5 mg/ml) did not affect PREG yield, nor did they alter basal and ACTH-stimulated post-PREG output of both ZG and ZF/ZR cells; however, they elicited a marked decrease in ANG-II-enhanced production of 18-hydroxylated steroid by AG cells. Concentrations of CSA higher than 0.5 mg/ml strikingly reduced either basal and agonist-stimulated over-all steroidogenesis of both ZG and ZF/ZR cells. These findings suggest that CSA at low concentrations strongly stimulates the conversion of cholesterol to PREG (i.e. the rate-limiting step of steroidogenesis), while at middle concentrations it did not affect this early step, but specifically interferes with the intracellular events which transduce the stimulatory signal of ANG-II on the late steps of mineralocorticoid production (i.e. the conversion of B to ALDO). At higher concentrations, CSA probably exerts a cytotoxic effect.

Adrenal Cortex↗

PubMed1994

The possible involvement of galanin in the modulation of the function of rat pituitary-adrenocortical axis under basal and stressful conditions.

The effect of a s.c. bolus injection of 2 micrograms galanin on the hypothalamo-pituitary-adrenocortical (HPA) axis were investigated in both normal and ether-stressed (2 min ether-vapor inhalation) or cold-stressed (20 min at 4 degrees C) rats. Blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA, 1, 2 or 4 h after galanin injection. Galanin administration to normal rats resulted in a marked rise in the blood levels of ACTH, ALDO and B at 1h and 2 h, the values returned to the baseline after 4 h. Ether and cold stresses notably raised the blood levels of ACTH, ALDO and B, and these rises lasted unchanged until 4 h. Galanin markedly potentiated ACTH and ALDO responses to ether stress at 1 and 2 h, but B response remained unchanged. ACTH response to cold stress was not affected by galanin; however, galanin magnified ALDO response to cold stress at 4 h, and enhanced at 1 h and depressed at 2 h that of B. In light of these findings the following conclusions can be drawn: (i) galanin exerts a stimulatory effect on HPA axis of rats under basal conditions; (ii) under our experimental conditions, ether stress exerts a stronger stimulation of HPA axis than cold stress; (iii) the galaninergic mechanisms involved in the stimulation of ACTH release do not interfere with ether stress-activated ones controlling ACTH secretion, and are probably similar to those underlying the effect of cold stress; (iv) steroidogenic capacity of adrenal cortex, at least in term of glucocorticoid hormones, is a rate-limiting step in the response of rat HPA axis to severe stresses; and (v) galanin exerts a direct secretory action of the rat adrenal gland, that can manifest itself only in the case of submaximally cold stress-stimulated HPA axis.

Adrenal Cortex↗

PubMed1994

Different effects of neurotensin and neuromedin-N on the proliferative activity of rat adrenal cortex.

Evidence indicates that neurotensin (NT) and neuromedin-N (NMN) exerts an adrenocorticotropic effect in the rat. The present study aimed to investigate whether these neuropeptides are able to stimulate the proliferation of rat adrenocortical cells in vivo and to compare their mode of action. Adrenocortical proliferative activity was assessed by the metaphase-arrest technique and metaphases were counted per medulla-containing adrenal section. A bolus administration of NT (3 micrograms/rat) resulted in a significant increase in the number of metaphases in both zona fasciculata and the entire cortex, an effect observed 48 h after the injection. The administration of NMN (3 micrograms/rat) induced a notable rise in the number of metaphases in the zona fasciculata and the entire cortex within 12 h, followed by a subsequent drop after 24 h and a return to normal values at 48 h. These findings indicate that NT and NMN enhance rat adrenal growth in vivo acting via different mediators.

Adrenal Cortex↗

PubMed1994

Neuromedins and their involvement in the regulation of growth, structure and function of the adrenal cortex.

Current data on the synthesis and the mechanism of action of neuromedins on adrenal cortex are presented. The localization of these biologically-active peptides in all components of the hypothalamopituitary-adrenal axis as well as their action on the adrenal cortex both in vivo and in vitro suggest their involvement in the regulation of growth, structure and function of the adrenal cortex. Neuromedins may exert both direct and indirect effect on the adrenal cortex. Direct effect is proven by the stimulation of glucocorticoid synthesis by adrenocortical cells in culture (NMK, NML) while indirect effects may be mediated by ACTH, vasopressin (aldosterone secretagogue effect) and angiotensin (prompt proliferative response) or by substances of medullary origin. The last mechanism of action is well documented for NMU.

Adrenal Cortex↗

PubMed1993

Arginine-vasopressin release mediates the aldosterone secretagogue effect of neurotensin in rats.

Acute and chronic systemic administrations of neurotensin (NT) and arginine-vasopressin (AVP) significantly increases plasma aldosterone concentration (PAC) in rats. Deamino-Pen1, Val4, D-Arg8-vasopressin (AVP-A), a potent AVP antagonist, completely reversed both acute and chronic aldosterone secretagogue actions of NT and AVP. AVP-A acute administration did not affect basal PAC, while chronic AVP-A treatment significantly lowered it. Taken together our findings suggest that both NT and AVP exert a marked aldosterone secretagogue effect in rats, and that the mechanism underlying NT action may involve the stimulation of AVP release. Moreover, they indicate that endogenous AVP plays an essential role in the maintenance of the mineralocorticoid secretory capacity of rat zona glomerulosa.

Aldosterone↗

PubMed1993

Effects of neuromedin-N on the pituitary-adrenocortical axis of dexamethasone-suppressed rats.

Neuromedin-N (NMN) (6 micrograms/100 g body weight for 2 d) partially reversed the dexamethasone (Dx)-induced inhibition of ACTH release and the consequent adrenal atrophy and decrease in glucocorticoid (corticosterone) plasma concentration in rats. Dx administration did not alter the level of circulating mineralocorticoid (aldosterone), but NMN (2 or 6 micrograms/100 g body weight for 2 d) significantly increased it. These findings suggest that the mechanism underlying the glucocorticoid (but not the mineralocorticoid) secretagogue action of NMN involves the stimulation of hypophyseal ACTH release. The hypothesis is advanced that the potent mineralocorticoid secretagogue effect of NMN may be mediated either by a direct action on zona glomerulosa cells or by the enhanced release of other regulatory peptides exerting aldosterone stimulating effect.

Adrenocorticotropic Hormone↗

PubMed1993

Unusual effect of prolonged vasoactive intestinal peptide (VIP) administration on the adrenal growth and corticosterone secretion in the rat.

VIP is widely distributed in the body, and among others is present within the hypothalamo-pituitary-adrenal axis. The aim of this study was to investigate the effect of prolonged VIP administration on the structure and function of the rat adrenal cortex. Adult female rats were treated for 7 or 14 days with VIP (1.5 micrograms/100 g/day). This treatment did not change adrenal weight and evoked only slight changes in the stereologic parameters of adrenal cortex (volume of adrenocortical zones, average cell volume and number of cells in the gland). On the contrary, basal plasma corticosterone levels were markedly lowered (44% and 26% of control values in 7- and 14-day experiments, respectively), an effect accompanied by a significant decrease in corticosterone output by adrenal slices. After standardized ether stress, blood corticosterone concentration was similar in control and 14-day VIP-treated rats, while corticosterone secretion by adrenal quarters was higher in VIP-administered animals. Thus, prolonged VIP administration results in an unusual inhibition of corticosterone secretion in the rat, which is not coupled with a compensatory hypertrophy of the rat adrenal cortex. Such changes may depend on a modulatory action of VIP on the hypothalamo-pituitary-adrenal axis, and its possible mechanism is discussed.

Adrenal Cortex↗

PubMed1993

Evidence that endogenous arginine-vasopressin (AVP) is involved in the maintenance of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

A 7-day subcutaneous infusion with the AVP antagonist [Deamino-Pen1, Val4, D-Arg8]-vasopressin (AVP-A; 3 nmol.kg-1 x min-1) significantly lowered plasma aldosterone concentration in rats, without affecting the plasma levels of ACTH and corticosterone. Prolonged AVP-A treatment caused a marked atrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells, without inducing any significant change in zona fasciculata morphology. Isolated ZG cells from AVP-A-infused rats evidenced a notable decrease in both their basal and maximally-stimulated aldosterone production. The simultaneous infusion of rats with AVP (3 nmol.kg-1 x min-1) completely reversed all these effects of AVP-A. These findings suggest that endogenous AVP may be specifically involved in the maintenance of the growth and steroidogenic capacity of rat adrenal ZG. Moreover, they seem to indicate that under basal conditions the pituitary-adrenal-glucocorticoid axis is independent of AVP release.

Adrenocorticotropic Hormone↗

PubMed1993

Stereologic studies on the long-term effect of prazosin on rat adrenal cortex.

Adult female rats were treated with prazosin, a selective alpha 1-adrenoceptor inhibitor, for 60 days in doses of 0.5 mg/kg/day or 0.5 mg/kg/8 h. Prolonged prazosin administration lowered the gain of body weight and significantly decreased systolic blood pressure and heart weight. Prazosin administered every 8 h also lowered serum triglycerides but did not change the total cholesterol level. Selective alpha 1-inhibitor treatment increased the adrenal gland weight and decreased the number of adrenocortical cells; in every 8 h treated group this effect being connected with a marked cell hypertrophy (in all adrenocortical zones). Our results suggest that prazosin induced changes in the structure of the rat adrenal cortex depend on activation of the hypothalamo-pituitary-adrenocortical axis and possibly on the small inhibition of the proliferative activity of rat adrenocortical cells.

Adrenal Cortex↗

PubMed1993

Thyrotropin-releasing hormone inhibits glucocorticoid secretion of rat adrenal cortex: in vivo and in vitro studies.

The bolus iv administration of TRH dose-dependently decreased ACTH-enhanced plasma corticosterone (B) concentration in rats, without affecting the basal one. The effects of TRH on steroid secretion of dispersed rat inner adrenocortical cells were investigated by HPLC. TRH significantly decreased both basal and ACTH-stimulated post-11-deoxycorticosterone (DOC) secretion (i.e. 18-hydroxy-DOC and B) and concomitantly raised DOC and progesterone release, so that the total postpregnenolone yield of our preparations was unaffected. TRH did not alter either basal or ACTH-stimulated pregnenolone production by isolated rat adrenocortical cells. It was concluded that TRH is an inhibitor of glucocorticoid secretion in rats, which electively impairs the late steps of B synthesis (i.e. 11- and 18-hydroxylation) without affecting the earlier steps, including the rate-limiting one of this process.

18-Hydroxydesoxycorticosterone↗

PubMed1993

Cytological aspects of the human adrenal cortex development in the course of intra-uterine life.

Stereological studies were performed on 20 pairs of adrenal glands of human foetuses. The volume of particular adrenocortical zones, average cell volume and number of parenchymal cells were calculated. In 50 to 320 mm crown-rump length (C.-R.L.) foetuses (9-38 weeks of the intra-uterine life) an exponential increase in adrenal gland weight was found. If compared with the earlier period, the rate of increase was evidently higher beginning from the 20th week and depended mainly upon enlargement of the foetal zone, with less marked changes in the glomerulosa-fasciculata zone. The zona glomerulosa (ZG) and the outer zona fasciculata (ZF) began to delineate by the 20th week of gestation. Zona reticularis was not observed in our material. From the beginning of development, fasciculata cell volume was markedly higher than that of ZG cells and lower than foetal zona (ZX) cells. Until the 20th week of intra-uterine life the volume of glomerulosa-fasciculata zone (G-FZ) increased at a slow rate, while the rate of increase in volume of ZX was higher. After 20 weeks the rate of increase in volume of all adrenocortical zones was markedly higher (the same as that of the stroma). The volume of stroma in ZX markedly exceeded that in the remaining parts of the cortex. The average cell volume of ZG and ZF remained constant during the foetal period, while the average cell volume of ZX cells increased gradually from the 9th to the 20th foetal week and afterwards remained unchanged. (ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗

PubMed1993

Involvement of neuropeptides in the regulation of growth, structure and function of the adrenal cortex.

Current data on the influence of neuropeptides on the growth, structure and function of cells comprising the hypothalamo-pituitary-adrenal axis were presented and discussed. The action of vasopressin, oxytocin, neurotensin, bombesin, neuropeptide Y, substance P and VIP have been evaluated. The hypothesis has been introduced that in vivo effect of some neuropeptides on the structure and function of the adrenal cortex is mediated by vasopressin.

Adrenal Cortex↗

PubMed1993

Effects of bombesin and neuromedin-B on the proliferative activity of the rat adrenal cortex.

Bombesin (BM) and neuromedin-B (NMB) exert similar biological effects, acting via two functionally distinct BM-receptor subtypes. The present study aimed to investigate whether BM and NMB stimulate the proliferation of rat adrenocortical cells and to compare their mode of action. Adult female rats were treated with a single subcutaneous dose of 3 micrograms BM or NMB. Adrenocortical proliferative activity was assessed by the metaphase-arrest technique. BM administration resulted in a marked increase in the number of metaphases in zona glomerulosa (ZG) and zona fasciculata (ZF), and in the entire cortex. This increase appeared 24 h after injection in the ZG, and after 48 h in the ZF. NMB administration, on the other hand, caused a prompt increase in the number of metaphases in the ZG and entire cortex at 12 h, followed by a subsequent drop below the control level at 24 and 48 h of experiment. These findings indicate that BM and NMB enhance the proliferative activity of rat adrenocortical cells acting via different receptors or different mediators.

Adrenal Cortex↗

PubMed1992

The effects of ageing on the morphology and function of the zonae fasciculata and reticularis of the rat adrenal cortex.

The morphological counterpart of the well-known age-dependent marked impairment of glucocorticoid secretion of rat adrenals was investigated by use of morphometric techniques. For this purpose 4-, 8-, 16- and 24-month-old rats were studied. Despite the notable lowering of both basal and ACTH-stimulated production of corticosterone by collagenase-dispersed inner adrenocortical cells, ACTH and corticosterone plasma concentrations displayed significant increases with ageing. Zona fasciculata (ZF) and zona reticularis (ZR) showed a notable hypertrophy in aged rats, which was due to rises in both the average volume and number of their parenchymal cells. The hypertrophy of ZF and ZR cells was in turn associated with increase in the volume of the mitochondrial compartment and proliferation of smooth endoplasmic reticulum, i.e., the two organelles involved in steroid-hormone synthesis. All these morphologic changes, conceivably due to the chronic exposure to high levels of circulating ACTH, are interpreted as a response enabling ZF and ZR to compensate for their age-dependent lowering in glucocorticoid secretion. Stereology also demonstrated that ZF and ZR cells underwent a striking age-related lipid-droplet repletion. Lipid droplets are the intracellular stores of cholesterol esters, the obligate precursors of steroid hormones in rats. This finding is in keeping with the contention that the mechanism underlying the age-dependent decline in rat-adrenal glucocorticoid secretion mainly involves impairments of the utilization of intracellular cholesterol previous to its intramitochondrial transformation to pregnenolone.

Adrenocorticotropic Hormone↗

PubMed1992

Effects of galanin on the secretory activity of the rat adrenal cortex: in vivo and in vitro studies.

Galanin, a 28-amino-acid peptide originally isolated from pig intestine, was found to cause dose-dependent rises in the plasma concentration of corticosterone in hypophysectomized rats and in both basal and submaximally ACTH-stimulated in vitro corticosterone production by adrenal quarters and isolated zona fasciculata/reticularis cells. These findings indicate that galanin exerts a direct glucocorticoid secretagogue effect on the inner adrenocortical zones and suggest that galanin, high concentrations of which are contained in adrenal chromaffin cells, may be included in that group of regulatory peptides, by way of which adrenal zona medullaris is thought to exert a paracrine control on the function of the zona corticalis. Galanin was also found to increase the plasma level of aldosterone in hypophysectomized rats in a dose-dependent manner without inducing changes in natremia, kalemia, plasma renin activity, or ACTH plasma concentration. Galanin did enhance both basal aldosterone output and that following submaximal ACTH or angiotensin II stimulation aldosterone output from adrenal quarters, but not from isolated zona glomerulosa cells. This last, rather unexpected, result suggests that galanin exerts an indirect mineralocorticoid secretagogue action, which seems to require the structural integrity of the adrenal cortex and the presence of the adrenal medulla. The hypothesis is advanced that galanin may control the release of some medullary peptides, which in turn may affect mineralocorticoid secretion of the zona glomerulosa in a paracrine manner.

Adrenal Cortex↗