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G Mazzocchi

Publications and source records attributed to G Mazzocchi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Neuropeptide K and neurokinin A stimulate CRH and ACTH release by rat adrenal medulla in vitro.

Tachykinins are a family of peptides that are able to modulate the activity of the hypothalamo-pituitary CRH-ACTH system. Mammalian tachykinins include neurokinin A (NKA), neurokinin B (NKB), neuropeptide K (NPK), and substance P (SP). We investigated by RIA the effects of tachykinins on the release of CRH and ACTH by rat adrenal medulla in vitro. NKA and NPK concentration-dependently enhanced the release of both CRH and ACTH, NPK being more active than NKA. NKB exerted only a minor stimulatory action exclusively on CRH release, and SP was ineffective. The stimulatory effect of both NKA and NPK on ACTH release was blocked by the CRH receptor antagonist alpha-helical-CRH, thereby suggesting that the increase in ACTH secretion is consequent to the stimulation of CRH release. These findings indicate that NKA and NPK are stimulators not only of the central (hypothalamo-pituitary), but also of the peripheral (intramedullary) branch of the CRH-ACTH system.

Adrenal Medulla↗
PubMed1997

Endothelins stimulate deoxyribonucleic acid synthesis and cell proliferation in rat adrenal zona glomerulosa, acting through an endothelin A receptor coupled with protein kinase C- and tyrosine kinase-dependent signaling pathways.

The effects of endothelins (ET) on the proliferative activity of the rat adrenal cortex have been investigated in vivo, using an in situ perfusion technique of the intact left gland. The chemicals were dissolved in the perfusion medium, and the perfusion continued for 120 min. ET-1 concentration dependently increased the mitotic index and [3H]thymidine incorporation into DNA in the zona glomerulosa (ZG; 6- and 3-fold increases, respectively, at a 10(-8) M concentration), but not in the inner adrenocortical layers, where the basal proliferative activity was negligible. The effect of 10(-8) M ET-1 was blocked by the ETA receptor antagonist BQ-123, whereas the ETB receptor antagonist BQ-788 was ineffective. ET-2 and ET-3 (10(-8) M) enhanced DNA synthesis in the ZG, but their effects were less intense than that of 10(-8) M ET-1 and were directly related to their binding potency for the ETA receptor subtype (ET-1 > ET-2 >> ET-3). The selective ETB receptor agonists BQ-3020, IRL-1620, and sarafotoxin-6B were ineffective. The ZG proliferogenic action of 10(-8) M ET-1 was reversed by both the protein kinase C inhibitor Ro31-8220 and the tyrosine kinase inhibitor tyrphostin-23; a complete blockade was obtained at a 10(-6)-M concentration of each inhibitor. In contrast, neither the protein kinase A inhibitor H-89 (10(-5) M) nor the cyclooxygenase and lipoxygenase inhibitors indomethacin and phenidone (10(-5) M) affected ET-1 action. Collectively, our findings indicate that ETs stimulate the proliferation of rat adrenal ZG cells, acting through ETA receptors coupled with protein kinase C- and tyrosine kinase-dependent signaling pathways. The results of the present study are in keeping with the view that in mammals, ZG is the proliferative layer involved in the maintenance of growth of the entire adrenal cortex and with the previous autoradiographic demonstration that ZG is the only adrenocortical layer provided with ETA receptors.

Animals↗
PubMed1997

Angiotensin-II stimulates DNA synthesis in rat adrenal zona glomerulosa cells: receptor subtypes involved and possible signal transduction mechanism.

Using an in situ perfusion technique of isolated left rat adrenal gland, it has been demonstrated that angiotensin-II (ANG-II) increases DNA synthesis in the zona glomerulosa (ZG), but not fasciculata-reticularis cells. The AT1 receptor antagonist DuP753 abolished the effect of ANG-II, while the AT2 receptor antagonist PD 123319 potentiated it. Both Ro31-8220, an inhibitor of protein kinase C (PKC), and tyrphostin-23, an inhibitor of tyrosine kinase (TK), evoked a partial reversal of ANG-II effect, and when added together to the perfusion medium abolished it. In contrast, the phospholipase C inhibitor U-73122 alone was able to induce a complete blockade of ANG-II effect. Neither the phospholipase A2 inhibitor AACOCF3 nor the cyclooxygenase inhibitor indomethacin and the lipoxygenase inhibitor phenidone affected ANG-II-induced stimulation of DNA synthesis, thereby making unlikely the involvement of the arachidonic acid signaling pathways. Our findings suggest that (i) ANG-II stimulates rat ZG cell proliferation acting via AT1 receptors coupled with phospholipase C, which activates both PKC and TK signaling systems; and (ii) the proliferogenic effect of ANG-II is partially counteracted by the activation of the AT2 receptor subtype.

Angiotensin II↗
PubMed1996

Evidence that both ETA and ETB receptor subtypes are involved in the in vivo aldosterone secretagogue effect of endothelin-1 in rats.

Endothelins (ET) are a family of vasoconstrictor peptides, secreted by vascular endothelium, which act through two main subtypes of receptors: ETA and ETB. ET-1 is known to stimulate aldosterone (ALDO) secretion by adrenal zona glomerulosa (ZG), and in vitro its effect was recently found to be exclusively mediated by ETB receptors. In this study the involvement of ETA and ETB in the mediation of the in vivo acute ALDO secretagogue action of ET-1 was investigated by the use of their selective antagonists BQ-123 and BQ-788, respectively. The bolus intraperitoneal administration of ET-1 dose-dependently raised both basal and angiotensin II (ANG II)-enhanced plasma ALDO concentration (PAC) in rats. Both antagonists counteracted the stimulatory effect of ET-1 on basal PAC, and when administered together completely annulled it. Conversely, only BQ-788 reversed the effect of ET-1 on ANG II-enhanced PAC. ET-1 increased systolic blood pressure (BP) in normal rats, but not in animals simultaneously administered ANG II. The hypertensive effect of ET-1 was completely abolished by BQ-123, and not affected by BQ-788. In light of these findings the following conclusions can be drawn: (i) the in vivo ALDO secretagogue action of ET-1 is mediated by both ETA and ETB, this latter subtype of ET receptors playing a major role; and (ii) the mechanism whereby ETA participates in this in vivo effect of ET-1 is indirect, and probably connected with the ET-1-induced rise in BP and adrenal blood flow.

Adrenal Cortex↗
PubMed1996

Adrenomedullin and calcitonin gene-related peptide inhibit aldosterone secretion in rats, acting via a common receptor.

Adrenomedullin (ADM) and calcitonin gene-related peptide (CGRP) did not affect either basal or ACTH-stimulated secretion of a1dosterone and corticosterone by dispersed rat capsular and inner adrenocortical cells, respectively. However, both peptides strongly depressed angiotensin-II (ANG- II)-stimulated a1dosterone production by capsular cells, the minimal effective concentration was 10(-7) M. The inhibitory effect of both ADM and CGRP was reversed by CGRP8-37, a specific CGRP1 receptor antagonist; a complete reversal was obtained with a CGRP8-37 concentration of 10(-6) M. Our findings indicate that ADM and CGRP specifically interfere with the intracellular mechanisms transducing the secretagogue signal of ANG-II, and suggest that the ADM effect is mediated by CGRP receptors

Adrenocorticotropic Hormone↗
PubMed1996

Intra-adrenal 11 beta-hydroxysteroid dehydrogenase plays a role in the regulation of corticosteroid secretion: an in vitro study in the rat.

The expression of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) has been demonstrated in the adrenal glands, but until now little attention has been paid on its possible physiologic action. In-situ perfused rat adrenals released under basal conditions, in addition to mineralo- and glucocorticoids, notable amounts of 11-dehydrocorticosterone (DH-B), the inactive form to which corticosterone (the main glucocorticoid in rodents) is converted by 11 beta-HSD. The addition to the perfusion medium of glycyrrhetinic acid, a specific inhibitor of 11 beta-HSD, strongly reduced DH-B release and simultaneously evoked a moderate rise in both mineralo- and glucocorticoid output. The bolus administration of ACTH strikingly enhanced mineralo- and glucocorticoid secretion, but it significantly depressed DH-B release Rat adrenal microsome preparations possessed 11 beta-HSD activity, that was inhibited by glycyrrhetinic acid. Conversely, ACTH was without any apparent effect, a finding indicating that the in vivo observed ACTH-induced inhibition of adrenal 11 beta-HSD activity is mediated by an indirect mechanism whose elucidation requires further investigation. In conclusion, our present findings suggest that adrenal 11 beta-HSD plays a role in the regulation of steroid secretion in rats under both basal and stimulated conditions.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Adrenomedullin stimulates steroid secretion by the isolated perfused rat adrenal gland in situ: comparison with calcitonin gene-related peptide effects.

Adrenomedullin (ADM), a vasodilatatory peptide contained in adrenal medulla, was found to induce a dose-dependent increase in aldosterone (ALDO) and corticosterone (B) release by the in situ perfused rat adrenal gland, along with a rise in the flow rate of the perfusion medium. The minimal effective dose for ALDO response was three and two orders of magnitude less than those able to evoke B and medium flow rate responses. Calcitonin gene-related peptide (CGRP), another vasodilatatory peptide contained in adrenal medulla and showing a slight homology in its amino acid sequence with ADM, elicited similar effects. CGRP (8-37), a specific antagonist of CGRP1 receptors, annulled all the effects of both ADM and CGRP, whereas l-alprenolol, a beta-adrenoceptor antagonist, partially reversed only ALDO response to the peptides. In light of these findings the following conclusions are drawn: i) ADM and CGRP stimulate rat adrenals in vivo to release B by raising blood flow rate; ii) ADM and CGRP enhance ALDO secretion via an indirect mechanism probably requiring the release of catecholamines by medullary chromaffin cells; and iii) the effects of ADM and CGRP on the rat adrenal gland are mediated by a common receptor of the CGRP1 subtype.

Adrenal Glands↗
PubMed1996

Further investigations on the effects of neuropeptide Y on the secretion and growth of rat adrenal zona glomerulosa.

NPY is a regulatory peptide, high levels of which are contained in adrenal glands of several mammals and which is co-released with catecholamines during various stressful conditions. The acute and chronic effects of NPY on adrenocortical secretion and growth were studied in the rat. NPY concentration-dependently increased aldosterone (ALDO), but not corticosterone (B) secretion of adrenal slices (maximal effective concentration was 10(-7) M). Two competitive inhibitors of NPY receptors, named PYX-1 and PYX-2, were found to dose-dependently inhibit ALDO response of adrenal preparations to 10(-7) M NPY; PYX-2 was more efficient than PYX-1, and at a concentration of 10(-5) M completely annulled the effect of 10(-7) M NPY. The acute bolus intraperitoneal (i.p.) injection of NPY (3 nmol/kg) raised plasma ALDO concentration (PAC), but not that of B (PBC); this effect of NPY was blocked by the simultaneous injection of PYX-2 (300 nmol/kg). The prolonged i.p. infusion with NPY (3 nmol/kg/h for 7 days) increased PAC (but not PBC) and induced a marked hypertrophy of the zona glomerulosa (ZG) and its parenchymal cells; dispersed ZG cells obtained from NPY-infused rats displayed a significantly enhanced basal and maximally agonist-stimulated ALDO production. The simultaneous infusion with PYX-2 (300 nmol/kg/h) completely annulled all these effects of NPY. The acute or chronic administration of PYX-2 alone did not evoke any apparent effect on the ZG secretion and growth. In light of these findings the following conclusions can be drawn: (i) NPY is able to stimulate not only the secretion, but also the growth of adrenal ZG in rats, via a receptor-mediated mechanism (since this effect is blocked by PYX-2); (ii) endogenous NPY does not play a prominent role in the physiological maintenance of secretion and growth of rat ZG (since PYX-2 alone is ineffective); (iii) NPY may play a crucial role in the fine tuning of the ZG functions in conditions requiring an increased release of mineralocorticoid hormones.

Aldosterone↗
PubMed1995

Pancreatic polypeptide enhances plasma glucocorticoid concentration in rats: possible role in hypoglycemic stress.

The acute bolus intraperitoneal (i.p.) administration of pancreatic polypeptide (PP) dose-dependently enhanced the plasma concentration of corticosterone (PBC) in hypophysectomized/ACTH replaced rats, but not that of aldosterone. Minimal and maximal effective doses were 10(-12) and 10(-10) mol/rat, respectively, and maximal PBC increase occurred between 60 and 120 min after PP injection. Insulin (1 U/kg, i.p.) evoked a net decrease in the blood glucose concentration, and marked rises in the plasma levels of PP and PBC, that attained their maximum at 60 and 120 min, respectively. The effects of insulin were annulled by the simultaneous injection of 0.5 mg/kg atropine. The effects of 1 U/kg insulin and 10(-10) mol/rat PP on PBC were not additive; atropine did not affect PBC response to PP or PP plus insulin, though annulling that to insulin alone. Taken together these findings suggest that PP plays a physiologic role in the rat as modulator of the adrenal response to the insulin-induced hypoglycemic stress.

Aldosterone↗
PubMed1995

Evidence that endogenous substance-P (SP) is involved in the maintenance of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

A 7-day intraperitoneal infusion with the specific SP antagonist magnitude of D-Pro4,D-Trp7,9-SP4-11 (SP-A; 0.3 nmol.kg-1.min-1) significantly lowered plasma aldosterone (ALDO) concentration and caused atrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells. Dispersed ZG cells from SP-A-infused rats displayed a marked decrease in both their basal and maximally agonist-stimulated ALDO production. The simultaneous infusion of rats with SP (0.03 nmol.kg-1.min-1) completely annulled all these effects of SP-A. The plasma levels of ACTH and corticosterone, and the morphology of adrenal zona fasciculata were not affected by SP-A or SP-A plus SP infusion. These findings suggest that endogenous SP is specifically involved in the positive control of growth and secretion of the rat ZG.

Aldosterone↗
PubMed1995

Adrenal medulla is involved in the aldosterone secretagogue effect of substance P.

Substance P (SP) increased aldosterone secretion of rat adrenal slices, but not of isolated zona glomerulosa cells, and this effect was annulled by two specific antagonist of SP (SP-A). Both tissue preparations displayed an aldosterone secretory response to isoprenaline (IP) that was blocked by l-alprenolol (AL). AL reversed the aldosterone response of adrenal slices to IP, SP, or IP plus SP, whereas SP-A only suppressed that to SP. Quarters of adrenocortical autotransplants, which are completely deprived of chromaffin cells, showed an aldosterone response to IP, but not to SP. These findings suggest that the mechanism underlying the aldosterone secretagogue action of SP probably involves the stimulation of catecholamine release by adrenal medulla chromaffin cells.

Adrenal Cortex↗
PubMed1995

Morphology and function of the adrenal zona glomerulosa of transgenic rats TGR [mREN2] 27: effects of prolonged sodium restriction.

Heterozygous female transgenic rats for the murine Ren-2 gene (TGR) display a high blood pressure, together with a low kidney and high adrenal renin content. The effects of prolonged sodium restriction on the morphology and secretory activity of adrenal zona glomerulosa (ZG) of TGR and their age- and sex-matched Sprague-Dawley control rats (SDR) were investigated. Under basal conditions, TGR had a moderately hypertrophic ZG, that showed a significantly higher secretion of 18-hydroxylated (18OH) steroids: 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO); ZG cells of TGR showed angiotensin II (AII)-binding site concentrations and ALDO secretory responses to AII similar to those of SDR ZG cells. Prolonged sodium restriction increased plasma ALDO level in both SDR and TGR, and significantly raised the volume of ZG. ZG hypertrophy was due to the increase in both the number and average volume of its parenchymal cells. The secretion of 18OH-steroids was markedly enhanced in both groups of rats; however, in TGR this rise was exclusively due to increases of 18OH-DOC and 18OH-B, while in SDR also ALDO production was enhanced. The yield of non-18OH-steroids was not affected. 11-Dehydrocorticosterone production was not changed in SDR, but doubled in TGR. ZG cells of sodium-restricted SDR and TGR displayed similar increases in their AII-binding site concentration and ALDO secretory response to AII. In conclusion, our present findings confirm that TGR possess a hypertrophic ZG and an elevated secretory capacity o 18OH-steroids, but show only slight differences in ZG and ZG-cell responses to prolonged sodium deprivation.

Animals↗
PubMed1995

Bacterial lipopolysaccharide stimulates glucocorticoid secretion in hypophysectomized rats.

The effect of an i.p. bolus injection of 200 micrograms.kg-1 bacterial lipopolysaccharide (LPS) on the plasma concentrations of ACTH and corticosterone (B) were studied in intact and hypophysectomized/ACTH replaced (Hx) rats. Hormonal blood levels were measured by RIA, 30, 60, 120, 180 and 240 min after the injection. The stress evoked by the vehicle i.p. injection provoked significant rises in ACTH and B blood levels at 30 and 60 min in intact rats, but not in Hx animals. In intact rats, LPS enhanced (over the respective control value) ACTH plasma level at 60, 120 and 180 min, and B plasma concentration at 120, 180 and 240 min. In Hx rats, LPS did not affect ACTH blood level, but raised B plasma concentration at 60, 120 and 180 min. B response to LPS at 120 min was completely annulled, in both intact and Hx rats, by the simultaneous administration of 25 nmol.kg-1 alpha-helical-CRH and corticotropin-inhibiting peptide that are competitive inhibitors of CRH and ACTH, respectively. The hypothesis is advanced that LPS may activate hypothalamo-pituitary adrenal axis in rats, by stimulating not only the central (hypothalamo-pituitary), but also the peripheral (intra-adrenal) branch of the CRH/ACTH system.

Adrenocorticotropic Hormone↗
PubMed1994

Neuropeptide K enhances glucocorticoid release by acting directly on the rat adrenal gland: the possible involvement of zona medullaris.

Neuropeptide K (NPK), a member of the kassinin-like tachykinin family, is contained in the rat hypothalamus and is known to stimulate pituitary ACTH release. The intraperitoneal bolus administration of NPK dose-dependently enhanced corticosterone blood level not only in intact rats, but also in hypophysectomized/ACTH replaced animals. NPK did not affect corticosterone secretion of dispersed rat adrenocortical cells; however, it concentration-dependently raised basal corticosterone production by decapsulated adrenal quarters (including both cortical and medullary tissues). Minimal and maximal effective concentrations were 10(-9) and 10(-8) M, respectively. 10(-8) M NPK potentiated corticosterone response of adrenal quarters elicited by 10(-12) M ACTH, but not that evoked by higher concentrations of ACTH. The direct corticosterone secretagogue effect of 10(-8) M NPK is annulled by 10(-6) M alpha-helical-CRH or corticotropin-inhibiting peptide, competitive inhibitors of CRH and ACTH, respectively. In light of these findings, the hypothesis is advanced that NPK exerts a direct stimulatory action on adrenocortical secretion and that the mechanism underlying this effect of NPK may involve the activation of the intra-medullary CRH/ACTH system.

Adrenal Cortex↗
PubMed1994

Effect of hypophysectomy on corticotropin-releasing hormone and adrenocorticotropin immunoreactivities in the rat adrenal gland.

It has previously been shown that rat adrenal zona medullaris possesses an interleukin-1 beta (IL-1 beta)-responsive peripheral branch of the CRH/ACTH system that duplicates the hypothalamopituitary central one (Mazzocchi et al., Mol. Cell. Neurosci. 4: 267, 1993). The intraadrenal content of corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) immunoreactivities (ir), as well as IL-1 beta-stimulated release of CRH-ir and ACTH-ir, increased in relation to the number of days elapsed from hypophysectomy; the effect of hypophysectomy required at least 48 h to become significant and reached its maximum after 72 h. The action of IL-1 beta on ACTH-ir release was annulled by simultaneous exposure to alpha-helical-CRH, an antagonist of CRH. ACTH infusion, at a rate restoring a normal blood level of the hormone, prevented the effect of hypophysectomy on intraadrenal concentrations of both CRH-ir and ACTH-ir; similarly, the hypophysectomy-evoked rise in intraadrenal ACTH-ir content was completely annulled by treating hypophysectomized rats with CRH or dexamethasone. Taken together our findings suggest that the elimination of the central branch of CRH/ACTH system induces a marked increase in the activity of the intraadrenal peripheral one. The hypothesis is advanced that the hypophysectomy-induced lowering of circulating ACTH and the consequent drop in the production of adrenal glucocorticoids enhances, via a classic negative feedback mechanism, gene expression of CRH and ACTH in adrenal medullary chromaffin cells.

Adrenal Medulla↗
PubMed1994

Zona glomerulosa of the adrenal gland in a transgenic strain of rat: a morphologic and functional study.

Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess an increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.

Adrenocorticotropic Hormone↗