Vasoactive intestinal peptide stimulates rat adrenal glucocorticoid secretion, through an ACTH receptor-dependent activation of the adenylate cyclase signaling pathway.

Vasoactive intestinal peptide (VIP) concentration-dependently enhanced corticosterone and cyclic-AMP release by dispersed rat inner adrenocortical cells. A VIP-receptor antagonist and the ACTH-receptor antagonist corticotropin-inhibiting peptide annulled both adrenocortical-cell responses to VIP, while the protein kinase (PKA) inhibitor H-89 blocked only corticosterone response. Collectively, these findings suggest that VIP stimulates glucocorticoid secretion of rat adrenals, through the aspecific activation of ACTH receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway.

Endothelin-1, acting via the A receptor subtype, stimulates thymocyte proliferation in the rat.

Endothelins (ETs) are a family of vasoactive peptides widely distributed in the body systems, where they carry out major autocrine/paracrine regulatory functions, acting through two main subtypes of receptors (ETA and ETB). Evidence suggests that ETs play a permissive role in the development of neural crest-derived craniofacial structures, among which the thymus. Therefore, we have investigated whether ETs regulate thymocyte proliferation in the adult rat ET-1 (which binds both ETA and ETB receptors) increased the mitotic index (% of metaphase-arrested cells) in the thymus cortex, while ET-3 (which preferentially binds ETB) and the selective ETB-receptor agonists BQ-3020 and IRL-1620 did not.

A local immuno-endocrine interaction may mediate rat adrenal glucocorticoid response to bacterial endotoxins.

The effects of the bacterial endotoxin lipopolysaccharide (LPS) and interleukin (IL)-1beta on corticosterone secretion has been studied in vivo by employing the technique of in situ perfusion of the isolated rat left adrenal gland. Both LPS and IL-1beta dose-dependently raised corticosterone output, the response peaking at 60 and 90 min, respectively. IL-1 receptor antagonist dose-dependently reversed the effect of LPS and IL-1beta.

Pancreatic polypeptide stimulates rat adrenal glucocorticoid secretion by activating the adenylate cyclase-dependent signaling pathway.

Pancreatic polypeptide (PP) concentration-dependently raised basal corticosterone and cyclic-AMP production of dispersed rat zona fasciculata/reticularis adrenocortical cells, maximal effective concentration being 10(-7) M. 10(-7) M PP also significantly enhanced submaximally (10[-12]/10[-11] M), but not maximally (10[-9]/10[-8] M) ACTH-stimulated corticosterone and cyclic-AMP release. Corticosterone responses to PP were abolished by the specific protein kinase A (PKA) antagonist H-89 (10[-5] M).

The AT2 receptor-mediated stimulation of adrenal catecholamine release may potentiate the AT1 receptor-mediated aldosterone secretagogue action of angiotensin-II in rats.

The role played by AT1 and AT2 receptors in the mediation of angiotensin-II (ANG-II) aldosterone secretagogue action has been investigated in vitro using different types of rat adrenal preparations. ANG-II enhanced aldosterone secretion of dispersed zona glomerulosa (ZG) cells in a concentration-dependent manner (EC50, 3 x 10(-10) M), and its effect was annulled by the AT1-receptor antagonist DuP753 and unaffected by the AT2-receptor antagonist PD123319. ANG-II was significantly more effective in stimulating aldosterone secretion when capsule-ZG and adrenal slices containing medullary chromaffin cells were used (EC50, 1 x 10(-11) M and 7 x 10(-12) M, respectively); moreover, both DuP753 and PD123319 caused partial reversals (intense and moderate, respectively) of the responses to ANG-II, and when added together annulled them.

Distribution and functional significance of angiotensin-II AT1- and AT2-receptor subtypes in the rat adrenal gland.

The distribution and the functional significance of angiotensin-II (ANG-II) receptor subtypes, AT1 and AT2, in the rat adrenal gland has been investigated in vitro. Autoradiographic assessment of the selective displacement of [125I]ANG-II binding by selective ligands of the two receptor subtypes indicated that zona glomerulosa (ZG) was provided with both AT1 and AT2, and adrenal medulla (AM) almost exclusively with AT2 receptors. ANG-II (10(-9) M) evoked a marked rise in the secretion of aldosterone by dispersed ZG cells and catecholamines by AM fragments.

Paracrine control of steroid hormone secretion by chromaffin cells in the adrenal gland of lower vertebrates.

The adrenal glands of lower vertebrates display a notable intermingling between steroidogenic and chromaffin tissues, which increases from Pisces to Aves. As in mammals, adrenal chromaffin cells contain and release, in addition to catecholamines, serotonin and several peptides, which may affect the secretory activity of steroidogenic cells in a paracrine manner. Stimulatory molecules include serotonin, arginine-vasotocin, tachykinins, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide; inhibitory molecules are dopamine, somatotropic hormone-release inhibiting hormone and galanin.

Role of endothelins in regulation of vascular tone in the in situ perfused rat adrenals.

This study examined the role of endothelins (ETs) and their receptor subtypes ETA and ETB in the regulation of vascular tone in the in situ perfused rat left adrenal gland. Endothelin-1 (ET-1), which binds both ETA and ETB receptors, decreased adrenal flow rate of the perfusion medium, and its effect was reversed by the ETA antagonist BQ-123 and enhanced by the ETB antagonist BQ-788. ET-3, which preferentially binds ETB, and the selective ETB agonist BQ-3020 increased adrenal flow rate of perfusate, and their effects were annulled by BQ-788.

Effects of endothelin-1 on the rat pituitary-adrenocortical axis under basal and stressful conditions.

Endothelins (ETs) and their receptor subtypes A and B (ETA and ETB) are expressed in the various components of the mammalian hypothalamo-pituitary-adrenal (HPA) axis, but their involvement in the functional regulation of HPA is controversial. To gain insight into this topic, we have investigated the effects of ET-1 and/or the specific antagonists of ETA and ETB receptors (BQ-123 and BQ-788, respectively) on the plasma concentrations of ACTH, corticosterone and aldosterone of non-stressed (control) and ether- or cold-stressed rats. The study of the effects of the administration of the two ET-receptor antagonists alone could provide informations about the possible action of endogenous ETs on the HPA axis.

Effects of recombinant murine leptin on steroid secretion of dispersed rat adrenocortical cells.

Leptin is a peptide secreted by adipose tissue, which regulates satiety, metabolic rate, and thermogenesis. Since corticosteroids regulate the mass of adipose tissue, and leptin synthesis and secretion by adipocytes, we have examined whether leptin in turn is able to directly affect adrenal steroid secretion. Recombinant murine leptin was found to increase basal aldosterone and corticosterone production by dispersed rat zona glomerulosa and zona fasciculata-reticularis cells, respectively.

Effect of luteinizing hormone-releasing hormone on rat adrenocortical cells.

The effects of luteinizing hormone-releasing hormone (LH-RH) on the function of rat adrenal cortex were investigated by using dispersed zona glomerulosa (capsular) and zona fasciculata-reticularis (inner) cells. LH-RH increased basal (but not adrenocorticotropic hormone (ACTH)-stimulated) corticosterone secretion of inner cells, without affecting either aldosterone or corticosterone production by capsular cells. LH-RH markedly raised basal (but not ACTH-enhanced) cyclic-AMP release by inner cells.

Proadrenomedullin N-terminal 20 peptide inhibits aldosterone secretion of human adrenocortical and Conn's adenoma cells: comparison with adrenomedullin effect.

Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two vasoactive peptides, which are highly expressed in human adrenal gland. Autoradiography showed the presence of abundant [125I]ADM and [125I]PAMP binding sites in both the outer cortex and medulla of human adrenals. ADM, but not PAMP binding was completely displaced by the specific CGRP1 receptor antagonist CGRP(8-37).

Endothelin-1 stimulates steroid secretion of human adrenocortical cells ex vivo via both ETA and ETB receptor subtypes.

The role played by endothelins (ETs) and their receptor subtypes (ETA and ETB) in the regulation of steroid hormone secretion in human adrenal gland remains unclear. Therefore, we investigated the gene expression of ET-1 and its receptors in highly pure preparations of human adrenocortical cells and the effect of ET-1 on their secretory activity. Reverse transcription-PCR with primers specific for prepro-ET-1, ET-converting enzyme-1, ETA, and ETB complementary DNAs demonstrated the expression of all of these genes in human adrenocortical cells.

Autocrine-paracrine role of endothelin-1 in the regulation of aldosterone synthase expression and intracellular Ca2+ in human adrenocortical carcinoma NCI-H295 cells.

The role played by endothelin (ET-1) and its receptor subtypes A and B (ET(A) and ET(B)) in the functional regulation of human NCI-H295 adrenocortical carcinoma cells has been investigated. Reverse transcription-PCR with primers specific for prepro-ET-1, human ET-1 converting enzyme-1, ET(A), and ET(B) complementary DNAs consistently demonstrated the expression of all genes in NCI-H295 cells. The presence of mature ET-1 and both its receptor subtypes was confirmed by immunocytochemistry and autoradiography, respectively.

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.

Effects of pneumadin (PNM) on the adrenal glands. 6. Further studies on the inhibitory effect of PNM on dexamethasone-induced atrophy of the rat adrenal cortex.

Pneumadin (PNM) is a biologically active decapeptide, which has previously been found to enhanced rat adrenal growth; the mechanism is indirect and probably involves the stimulation of both arginine-vasopressin (AVP) and ACTH release. The effects of 2- and 6-day PNM administration on the atrophic adrenal cortices of rats treated for 8 and 12 days, respectively, with daily subcutaneous injections of 15 or 40 g/100 g body weight of dexamethasone (Dx) were investigated. Morphometry showed that PNM counteracted Dx-induced adrenal atrophy, by preventing the decrease in volume and number of the parenchymal cells.

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.

Distribution and functional significance of the endothelin receptor subtypes in the rat adrenal gland.

Endothelins (ET) are a family of vasoactive peptides that act via two subtypes of receptors, named ETA and ETB. ET-1 binds to both ETA and ETB, whereas the isopeptide ET-3 preferentially binds to ETB. The localization of ETA and ETB receptors in the rat adrenal gland and their involvement in the adrenal secretagogue effect of ETs has been studied in vitro.

Effects of adrenomedullin on the human adrenal glands: an in vitro study.

Numerous lines of evidence indicate that adrenal medulla exerts a paracrine control on the secretory activity of the cortex by releasing catecholamines and several regulatory peptides. Adrenomedullin (ADM) is contained in adrenal medulla of several mammalian species, including humans. Thus, we investigated whether human ADM1-52 exerts a modulatory action on steroid secretion of human adrenal cortex in vitro.

Neurotensin stimulates CRH and ACTH release by rat adrenal medulla in vitro.

Neurotensin (NT) is a 13-amino acid peptide, widely distributed in the central and peripheral nervous system, which is able to stimulate the activity of the hypothalamo-pituitary CRH-ACTH system. We investigated by RIA the effect of NT on the release of CRH and ACTH immunoreactivities (ir) by rat adrenal medulla in vitro. NT enhanced the release of both CRH-ir and ACTH-ir, the maximal effective concentration being 10(-8) M.

Stimulatory effect of the substance P antagonist spantide-II on aldosterone secretion of dispersed rat zona glomerulosa cells.

Substance P (SP) did not affect either basal or agonist-stimulated aldosterone production by dispersed rat zona glomerulosa (ZG) cells. In contrast, the SP-receptor antagonist spantide-II (SPA), at 10(-8)/10(-6) M concentrations, markedly raised basal and 10(-9) M ACTH, but not 10(-9) M angiotensin II-stimulated aldosterone secretion. The secretagogue effect of 10(-6) M SPA was annulled by SP (10(-6) M) and the protein kinase (PK)-C inhibitor Ro31-8220 (10(-6) M), but was unaffected by the PKA inhibitor H-89 (10(-5) M).

Role of adrenomedullin and related peptides in the regulation of the hypothalamo-pituitary-adrenal axis.

Adrenomedullin (ADM) is a hypotensive peptide, originally isolated from human pheochromocytomas, and then found to be widely distributed in the various body systems. ADM derives from preproadrenomedullin, a 185-amino acid residue prohormone, containing at its N-terminal a 20-amino acid sequence, named proadrenomedullin N-terminal 20 peptide (PAMP). ADM and PAMP immunoreactivities have been detected in the hypothalamo-pituitary-adrenal (HPA) axis of humans, rats, and pigs.

Different mechanisms mediate the in vivo aldosterone and corticosterone responses to 5-bromo-2'-deoxyuridine in rats.

The subcutaneous injection of 5'-bromo-2' deoxyuridine (BrdU) was found to raise the plasma concentrations of ACTH, aldosterone and corticosterone in rats. The aldosterone response was observed at a lower dose of BrdU and lasted for a longer period than those of ACTH and corticosterone (1.25 versus 2.