Biomedical subjects

G Mazzocchi

Publications and source records attributed to G Mazzocchi.

At least 73 records · Page 4Linked to original sources

PubMed1994

Evidence that endogenous somatostatin (SRIF) exerts an inhibitory control on the function and growth of rat adrenal zona glomerulosa. The possible involvement of zona medullaris as a source of endogenous SRIF.

The effect of SRIF and its antagonist cyclo(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr magnitude of Bzl)(SRIF-A) were studied in sham-operated and bilaterally adrenalectomized rats bearing ACTH- and angiotensin II (ANG-II)-responsive adrenocortical autotransplants. SRIF-A (10(-5) M) completely annulled SRIF (10(-6) M)-induced inhibition of ANG-II (10(-8) M)-evoked rise in aldosterone (ALDO) secretion by both dispersed zona glomerulosa (ZG) cells and autotransplant slices. A 7-day intraperitoneal infusion with SRIF (0.3 nmol.kg-1.min-1) significantly lowered plasma ALDO concentration (PAC) in both groups of animals, without affecting plasma renin activity and the plasma levels of ACTH and corticosterone. This treatment caused a marked atrophy of adrenal ZG and its parenchymal cells (without inducing any significant change in the zona fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant slices from SRIF-infused rats evidenced a notable decrease in both their basal and maximally ACTH- or ANG-II-stimulated ALDO production. The simultaneous infusion of rats with SRIF-A (3 nmol.kg-1.min-1) completely reversed all these effects of SRIF. The prolonged infusion with SRIF-A alone caused, in sham-operated rats, a marked increase in PAC and a significant hypertrophy of ZG and ZG cells; basal and maximally-stimulated ALDO secretion of dispersed ZG cells was also notably raised. Conversely, SRIF-A infusion did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous SRIF is specifically involved in the negative control of the secretion and growth of the rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to SRIF but not to SRIF-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal zona medullaris may be the source of endogenous SRIF regulating ZG function.

Adrenal Cortex↗

PubMed1994

Evidence that endogenous vasoactive intestinal peptide (VIP) plays a role in the maintenance of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

The effects of a 7-day intraperitoneal infusion with VIP (0.03 nmol.kg-1.min-1) and its antagonist [4-Cl-D-Phe6,Leu17]-VIP (VIP-A; 3 nmol.kg-1.min-1) were studied in sham and bilaterally adrenalectomized rats bearing ACTH and angiotensin II (ANG-II)-responsive adrenocortical autotransplants. VIP significantly increased plasma aldosterone (ALDO) concentration (PAC) and lowered plasma renin activity (PRA) in both groups of animals, without affecting plasma levels of ACTH and corticosterone. This treatment caused a marked hypertrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells (without inducing any significant change in the zona-fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant quarters obtained from VIP-infused rats evidenced a notable increase in both their basal and maximally ACTH- or ANG-II-stimulated ALDO secretion. The simultaneous infusion of rats with VIP-A completely reversed all these effects of VIP. The infusion with VIP-A alone caused, in sham-operated rats, a net decrease in PAC, coupled with a rise in PRA, and a marked atrophy of ZG and ZG cells; basal and maximally stimulated ALDO secretion of dispersed ZG cells was also significantly lowered. Conversely, VIP-A did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous VIP is specifically involved in the maintenance of the growth and secretory capacity of rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to VIP but not to VIP-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal medulla may be the source of endogenous VIP regulating ZG function.

Adrenocorticotropic Hormone↗

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↗

PubMed1993

Evidence that an extrahypothalamic pituitary corticotropin-releasing hormone (CRH)/adrenocorticotropin (ACTH) system controls adrenal growth and secretion in rats.

Within two weeks, hypophysectomy induced in rats a striking decrease in the level of circulating ACTH (the concentration of which was at the limit of sensitivity of our assay system), coupled with a net reduction in the plasma corticosterone concentration and an evident adrenal atrophy. Zona fasciculata, the main producer of glucocorticoids, was decreased in volume, due to a lowering in both the number and average volume of its parenchymal cells. Subcutaneous ACTH infusion (0.1 pmol.min-1), administered during the last week following hypophysectomy, restored the normal blood level of ACTH and completely reversed all effects of hypophysectomy on the adrenals. Subcutaneous infusion for one week with alpha-helical-CRH or corticotropin-inhibiting peptide (1 nmol.min-1), which are competitive inhibitors of CRH and ACTH, evoked a further significant lowering of plasma corticosterone concentration and markedly enhanced adrenal atrophy in hypophysectomized rats. These findings strongly suggest that an extrahypothalamic pituitary CRH/ACTH system may be involved in the maintenance of the growth and steroidogenic secretory activity of the rat adrenal cortex.

Adrenal Glands↗

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

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

A comparative study of the effect of atrial natriuretic peptide (ANP) on the secretory activity of rat adrenal cortex and angiotensin-II-responsive adrenocortical autotransplants.

Rat adrenocortical autotransplants regenerated from capsular-tissue fragments implanted in the musculus gracilis displayed an in-vitro basal gluco- and mineralocorticoid secretion qualitatively similar to that of adrenal quarters from control rats. Moreover, like adrenal quarters, they responded to angiotensin-II (Ang-II, 10(-8) M) by raising their yield of 18-hydroxylated steroids (18-hydroxy-11-deoxycorticosterone, 18-hydroxycorticosterone and aldosterone). ANP (10(-8) M), one of the main negative modulators of the zona-glomerulosa (ZG) mineralocorticoid secretion, totally blocked the ANG-II stimulating effect on adrenal quarters, but not that on adrenocortical autotransplants. Autoradiography showed that, in contrast with ZG cells of control rats, ZG-like cells of transplants did not significantly bind 125I-ANP. The hypothesis is discussed that ZG-like cells of regenerated adrenocortical nodules lack specific receptors for ANP.

Angiotensin II↗

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 interleukin-1 beta on the renin-angiotensin-aldosterone system in rats.

A bolus IP injection of interleukin-1 beta (IL-1 beta) (8 micrograms.kg-1) increased blood pressure and PRA without affecting plasma aldosterone (ALDO) concentration. IL-1 beta strongly attenuated angiotensin-II (ANG-II, 10(-8) M)-stimulated ALDO secretion by both isolated zona glomerulosa (ZG) cells and capsular strips. These findings suggest that IL-1 beta exerts a twofold opposite action on the main components of the rat renin-angiotensin-aldosterone system: simultaneous stimulation of renin release by kidneys and inhibition of the stimulatory effect of ANG-II on ALDO production. At the highest concentrations (10(-6)/10(-5) M), IL-1 beta was found to lower also basal ALDO output by isolated ZG cells, but not by capsular strips. However, in the presence of saralasin 10(-8) M (a competitive inhibitor of ANG-II) and captopril 10(-8) M (an angiotensin-I-converting enzyme inhibitor), IL-1 beta significantly reduced basal ALDO yield of capsular strips. These last results would suggest that IL-1 beta could also similarly affect the intra-adrenal renin-angiotensin system, which seems to be involved in the local regulation of ZG secretory activity.

Adrenal Glands↗

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↗

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

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

Direct secretagogue effect of corticotropin-releasing factor on the rat adrenal cortex: the involvement of the zona medullaris.

CRF dose-dependently enhanced corticosterone (B) secretion by rat adrenal slices including both cortex and medulla. Conversely, CRF did not exert any B response by fragments of adrenocortical autotransplants, which are completely deprived of chromaffin tissue. However, autotransplant quarters exhibited a dose-dependent response to ACTH qualitatively similar to that of adrenal slices, although markedly less intense. The maximal B response of adrenal slices to CRF (10(-8) M) was completely annulled by corticotropin-inhibiting peptide (10(-6) M), a competitive inhibitor of ACTH, which totally blocked the secretory response to ACTH (10(-8) M) of both kinds of preparations. ACTH immunoreactivity was present in the adrenal gland of control rats, but was undetectable in autotransplanted adrenocortical nodules. Moreover, adrenal fragments mainly composed of chromaffin tissue released detectable amounts of ACTH in response to high concentrations of CRF (10(-8)/10(-6) M). These findings suggest that chromaffin medullary cells play a pivotal role in the direct adrenocortical secretagogue effect of CRF, probably by releasing ACTH, which, in turn, may evoke, in a paracrine manner, the glucocorticoid response.

Adrenal Cortex↗

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↗

PubMed1991

Effects of prolonged sodium restriction on the morphology and function of rat adrenocortical autotransplants.

Regenerated adrenocortical nodules were obtained by implanting fragments of the capsular tissue of excised adrenal glands into the musculus gracilis of rats (Belloni et al. 1990). Five months after the operation, operated rats showed a normal basal blood level of corticosterone, but a very low concentration of circulating aldosterone associated with a slightly increased plasma renin activity (PRA). Regenerated nodules were well encapsulated and some septa extended into the parenchyma from the connective-tissue capsule. The majority of parenchymal cells were similar to those of the zonae fasciculata and reticularis of the normal adrenal gland, while zona glomerulosa-like cells were exclusively located around septa (juxta-septal zone; JZ). In vitro studies demonstrated that nodules were functioning as far as glucocorticoid production was concerned, while mineralocorticoid yield was very low. Prolonged sodium restriction significantly increased PRA and plasma aldosterone concentration, and provoked a marked hypertrophy of JZ, which was due to increases in both the number and average volume of JZ cells. Accordingly, the in vitro basal production of aldosterone and other 18-hydroxylated steroids was notably enhanced. The plasma level of corticosterone, as well as zona fasciculata/reticularis-like cells and in vitro production of glucocorticoids by regenerated nodules were not affected. These findings, indicating that autotransplanted adrenocortical nodules respond to a prolonged sodium restriction similar to the normal adrenal glands, suggest that the relative deficit in mineralocorticoid production is not due to an intrinsic defect of the zona glomerulosa-like JZ, but is probably caused by the impairment of its adequate stimulation under basal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

18-Hydroxydesoxycorticosterone↗