Neuromedin-U stimulates enucleation-induced adrenocortical regeneration in the rat.

Neuromedin-U (NMU) is a brain-gut peptide, which has been previously found to stimulate hypothalamic-pituitary-adrenal axis in the rat. Enucleation-induced adrenal regeneration in rats with contralateral adrenalectomy is a well-established model of adrenal growth, that not only depends on the compensatory ACTH hypersecretion, but is also modulated by several regulatory peptides. Hence, we investigated whether NMU may be included in this group of bioactive molecules.

In vitro and in vivo evaluation of acellular diaphragmatic matrices seeded with muscle precursors cells and coated with VEGF silica gels to repair muscle defect of the diaphragm.

In this work, a bioartificial system consisting of VEGF-loaded porous silica gel and myoblasts cultured on acellular diaphragmatic matrix (ADM) has been implanted to repair a surgically created diaphragmatic defect in Lewis rats. ADMs exerted a strong angiogenic response on chorio-allantoic membrane. Cytotoxicity, VEGF release and matrix erodibility in vitro tests demonstrated that the silica support was nontoxic and that the VEGF bioactivity was maintained after matrix entrapment and it was released within a timeframe that can be modulated by synthesis parameters.

Steroidogenic acute regulatory protein gene expression, steroid-hormone secretion and proliferative activity of adrenocortical cells in the presence of proteasome inhibitors: in vivo studies on the regenerating rat adrenal cortex.

Previous studies have shown that proteasome inhibitors promote the accumulation of steroidogenic acute regulatory protein (StAR) in cultured rat adrenocortical cells. Unexpectedly, this response was associated with a moderate lowering in the corticosterone secretion and proliferation rate of cultured cells. Hence, we studied the effects of proteasome inhibitors MG115 and MG132 on the secretion and proliferative activity of the regenerating adrenal cortex in rats 5 days after surgery.

Effects of neuromedin-U on immature rat adrenocortical cells: in vitro and in vivo studies.

Neuromedin U (NMU) is a brain-gut peptide, that in the peripheral organs and tissues acts via a G protein-coupled receptor, called NMUR1. Reverse transcription-polymerase chain reaction showed the expression of NMUR1 mRNA in either cortex and medulla or dispersed zona glomerulosa and zona fasciculata-reticularis cells of the immature rat adrenals. Accordingly, immunocytochemistry demonstrated the presence of NMUR1-like immunoreactivity in the cortex and medulla of immature adrenals.

Galanin stimulates cortisol secretion from human adrenocortical cells through the activation of galanin receptor subtype 1 coupled to the adenylate cyclase-dependent signaling cascade.

Previous studies showed that galanin receptors are expressed in the rat adrenal, and galanin modulates glucocorticoid secretion in this species. Hence, we investigated the expression of the various galanin receptor subtypes (GAL-R1, GAL-R2 and GAL-R3) in the human adrenocortical cells, and the possible involvement of galanin in the control of cortisol secretion. Reverse transcription-polymerase chain reaction detected the expression of GAL-R1 (but not GAL-R2 and GAL-R3) in the inner zones of the human adrenal cortex.

Up-regulation of adrenomedullin receptor gene expression in activated local stem cells during rat adrenal regeneration.

Previous studies showed that adrenomedullin (AM) gene expression was up-regulated in the regenerating rat adrenal cortex after enucleation and contra-lateral adrenalectomy, the effect being significant at day 1 after surgery and peaking between days 3 and 7. Using the same experimental model, we investigated by real time-polymerase chain reaction the mRNA expression of the AM receptor components: calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP)2 and 3. At time 0 (60 min after enucleation; control group), the CRLR mRNA content was approximately 2- and 5-fold higher than that of RAMP2 and RAMP3, respectively.

Cultured rat calvarial osteoblast-like cells are provided with orexin type 1 receptors.

Orexins A and B are hypothalamic peptides which are derived from the proteolytic cleavage of prepro-orexin and act via two subtypes of receptors, named OX1-R (that almost exclusively binds orexin-A) and OX2-R (nonselective for both orexins). Several lines of evidence show that other neuropeptides, which like orexins are involved in the central control of energy homeostasis (e.g.

Heterogeneity of aldosterone-producing adenomas revealed by a whole transcriptome analysis.

Aldosterone-producing adenomas (APAs) are a common cause of arterial hypertension, but the underlying molecular mechanisms are unknown, although a transcriptional modulation of aldosterone synthase (CYP11B2) has been suggested. Aldosterone synthesis involves 2 main rate-limiting steps: cholesterol transport into mitochondria and CYP11B2 gene transcription. Evidence supports a role of Ca(2+)/calmodulin-dependent protein kinases (CAMKs) in the regulation of angiotensin II- and potassium-stimulated aldosterone production.

Up-regulation of adrenomedullin gene expression in the regenerating rat adrenal cortex.

Adrenomedullin (AM) is an endogenous regulatory peptide that exerts growth-promoting action in several normal and neoplastic tissues, and we investigated whether its gene expression changes during rat adrenal regeneration after enucleation and contra-lateral adrenalectomy. Regenerating adrenals were collected at day 0 (just after enucleation; control rats), 1, 3, 7, 14 and 28 after surgery. The immunocytochemical assay of PCNA (proliferating cell nuclear antigen) index confirmed that the early stages of regeneration can be divided into an initial differentiation period (from day 0 to day 3) and a subsequent high proliferative period (days 5 and 7) followed by a decrease in the proliferation activity.

Leptin and the regulation of the hypothalamic-pituitary-adrenal axis.

Leptin, the product of the obesity gene (ob) predominantly secreted from adipocytes, plays a major role in the negative control of feeding and acts via a specific receptor (Ob-R), six isoforms of which are known at present. Evidence has been accumulated that leptin, like other peptides involved in the central regulation of food intake, controls the function of the hypothalamic-pituitary-adrenal (HPA) axis, acting on both its central and peripheral branches. Leptin, along with Ob-R, is expressed in the hypothalamus and pituitary gland, where it modulates corticotropin-releasing hormone and ACTH secretion, probably acting in an autocrine-paracrine manner.

Neuropeptide Y and glucocorticoid secretion from guinea pig adrenal gland: an in vivo and in vitro study.

The effects of neuropeptide Y (NPY) on adrenal glucocorticoid secretion are controversial, and we have investigated this issue in guinea pigs, where, like in humans and cows, the main glucocorticoid hormone is cortisol. In vivo experiments showed that prolonged NPY administration markedly lowered cortisol plasma concentration not only in normal guinea pigs, but also in animals whose hypothalamic-pituitary-adrenal axis and renin-angiotensin system had been pharmacologically interrupted by the simultaneous administration of dexamethasone and captopril. In vitro experiments ruled out the possibility that in vivo glucocorticoid anti-secretagogue action of NPY can ensue from a direct effect on the adrenal gland.

Expression of neuromedins S and U and their receptors in the hypothalamus and endocrine glands of the rat.

Neuromedin S (NMS) and neuromedin U (NMU) are regulatory peptides that share the C-terminal amino-acid sequence and act via common G protein-coupled receptors called NMUR1 and NMUR2. Semiquantitative real time-PCR showed that in the rat hypothalamus and testis NMS gene expression was markedly higher than that of the NMU gene, while the reverse occurred in the anterior pituitary and thyroid gland. Low expression of both genes was detected in the thymus, adrenal gland and ovary, whereas in the pancreatic islets only the expression of NMU mRNA was detected.

IGF-I enhances cortisol secretion from guinea-pig adrenal gland: in vivo and in vitro study.

Insulin-like growth factor (IGF)-I is a ubiquitously synthesized peptide that, along with IGF-II, acts via the IGF-R type I receptor. IGF-I and its receptor are expressed in the adrenal gland of humans and bovines, the secretion of which they seem to stimulate. As in humans and cows, the main glucocorticoid hormone secreted by guinea-pig adrenals is cortisol, and hence we have studied the adrenocortical effects of IGF-I in this species.

Nonclassic endogenous novel [corrected] regulators of angiogenesis.

Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch.

Tryptase- and leptin-positive mast cells correlate with vascular density in uterine leiomyomas.

Objective: In vitro and in vivo studies have linked mast cell (MC) degranulation and activation with angiogenesis and neovascularization. This assumption is partially supported by the close anatomical association between MC and the vasculature and the recruitment of these cells during tumor growth. The aim of this study was to correlate the extent of angiogenesis with the number of MC expressing tryptase and leptin in human leiomyomas.

On the role of receptor-receptor interactions and volume transmission in learning and memory.

Learning and memory seem to be inherent to a biological neural network. To emerge, they need an extensive functional connectivity, enabling a large repertoire of possible responses to stimuli, and sensitivity of the connectivity to activity, allowing for the selection of adaptive responses. According to the classical view about the organization of the CNS, the connectivity issue is realized by the huge amount of synaptic contacts each neuron establishes, while the adaptation of the network to specific tasks is obtained by mechanisms of activity-dependent synaptic plasticity.

Galanin in the regulation of the hypothalamic-pituitary-adrenal axis (Review).

Galanin is a regulatory 30- or 29-amino acid peptide, widely distributed in the nervous system and gut, that acts via three subtypes of G protein-coupled receptors, named GAL-R1, GAL-R2 and GAL-R3. Findings have been accumulated that galanin regulates neuroendocrine hypothalamic axes, including the hypothalamic-pituitary-adrenal (HPA) one. Galanin and its receptors are expressed in the hypothalamic paraventricular and supraoptic nuclei, anterior pituitary and adrenal medulla.

Evidence for a paracrine role of endogenous adrenomedullary galanin in the regulation of glucocorticoid secretion in the rat adrenal gland.

Previous investigations have shown that rat adrenocortical cells are provided with galanin receptors, and galanin stimulates glucocorticoid secretion from dispersed cells. The present study aimed to clarify the possible role of galanin in the physiological regulation of rat adrenal secretory activity. Reverse transcription-polymerase chain reaction detected galanin mRNA expression in the adrenal medulla, but not in the cortex.

Effects of neuropeptides B and W on the rat pituitary-adrenocortical axis: in vivo and in vitro studies.

Neuropeptides (NP) B and W are hypothalamic peptides involved in the regulation of feeding and neuro-endocrine axes. Evidence has been provided that NPB and NPW act on both the central and the peripheral branches of the rat hypothalamic-pituitary-adrenocortical axis, and we carried out in vivo and in vitro studies to gain insight into this topic. Reverse transcription-polymerase chain reaction showed the expression of NPB, NPW and their receptors in both adrenal cortex (zonae glomerulosa and fasciculata-reticularis) and adrenal medulla, where immunocytochemistry also detected the presence of abundant NPB- and NPW-immunoreactivity.

Galanin enhances corticosterone secretion from dispersed rat adrenocortical cells through the activation of GAL-R1 and GAL-R2 receptors coupled to the adenylate cyclase-dependent signaling cascade.

Galanin is a regulatory peptide, which acts via three subtypes of receptors, named GAL-R1, GAL-R2 and GAL-R3. Reverse transcription-polymerase chain reaction demonstrated the expression of GAL-R1 and GAL-R2, but not GAL-R3 mRNAs in dispersed rat adrenal zona fasciculata-reticularis (inner) cells. The immuno-blockade of GAL-R1 and GAL-R2, but not GAL-R3, decreased the binding of [3H]galanin to dispersed cells, a complete inhibition being obtained only by the simultaneous blockade of both receptor subtypes.

Vitamin C prevents zidovudine-induced NAD(P)H oxidase activation and hypertension in the rat.

Objective: Cardiovascular risk is increased among HIV-infected patients receiving antiretroviral therapy due to the development of hypertension and metabolic abnormalities. In this study, we investigated the effects of long-term treatment with zidovudine (AZT) and vitamin C, alone and in combination, on blood pressure and on the chain of events linking oxidative stress to cardiac damage in the rat.

Methods: Six adult Wistar Kyoto rats received AZT (1 mg/ml) in the drinking water for 8 months, six vitamin C (10 g/kg of food) and AZT, six vitamin C alone, and six served as controls.

Down-regulation of the beacon gene expression in the regenerating rat adrenal cortex.

Beacon, a hypothalamic peptide involved in the regulation of food intake, has been recently shown to be expressed in the adrenal cortex, and to inhibit its secretion and growth. To further characterize the role of beacon in the control of adrenal growth, we investigated the level of beacon gene expression in the regenerating rat adrenal cortex. Conventional reverse transcription-polymerase chain reaction (PCR) and immunocytochemistry demonstrated the expression of beacon mRNA and protein in the adrenals at both days 5 and 8 of regeneration after enucleation and contralateral adrenalectomy.

Endocrine disruptors and rat adrenocortical function: studies on freshly dispersed and cultured cells.

The effects of four endocrine disruptors: resveratrol, diphenylolpropane (bisphenol-A; BSP), benzophenone-3 (BP3) and silymarin on the secretory and proliferative activity of rat adrenocortical cells were investigated in vitro. Resveratrol and BP3 acutely increased basal corticosterone secretion from freshly dispersed adrenocortical cells, and resveratrol and BSP enhanced ACTH-stimulated cells. The 24-h exposure to resveratrol and BP3 increased basal corticosterone production from cultured adrenocortical cells, while ACTH-stimulated secretion was increased only by resveratrol.

Urotensin-II and its receptor (UT-R) are expressed in rat brain endothelial cells, and urotensin-II via UT-R stimulates angiogenesis in vivo and in vitro.

Urotensin-II (UII), along its receptor UT-R, is widely expressed in the cardiovascular system, where it exerts regulatory actions under both physiological and pathological conditions. Real-time PCR and immunocytochemistry demonstrated the expression of UII and UT-R as mRNA and protein in rat neuromicrovascular endothelial cells (NECs). UII did not affect the proliferation rate of cultured NECs, but exerted a strong angiogenic action in both an in vitro assay on Matrigel and an in vivo assay on chorioallantoic membrane.