neuropeptide-y and Hyperplasia

The purpose of this study was to explore the role of neuropeptide Y (NPY) on molecular and histological changes in human pituitary adenomas. The localization of NPY and its expression at the protein, messenger RNA (mRNA), and receptor levels were investigated here in different subcategories of pituitary adenomas. Immunohistochemical staining was performed in all cases to assess expression of NPY. Reverse transcription-polymerase chain reaction (RT-PCR) was used to study the mRNA expression of NPY. NPY subcellular localization was observed using immunoelectron microscopy in cytoplasm, rough endoplasmic reticulum, and cell matrix in four of the six cases of pituitary adenoma. NPY protein expression was observed in 59.6% of 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. mRNA expression of NPY was observed in all 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. Significantly different levels of expression were observed across different subcategories of pituitary adenoma. mRNA expression of Y1R and Y2R was observed across all subcategories of pituitary adenomas, and a positive correlation was observed between NPY and Y2R. In conclusion, evidence is provided here for the expression of NPY and its receptors, Y1R and Y2R, in human pituitary adenoma, and the levels of expression were found to differ across different subcategories. Differences in expression of Y2R in human pituitary adenomas were found to have remarkable statistical significance.

Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adolescent; Adult; Aged; Cytoplasm; Endoplasmic Reticulum, Rough; Female; Growth Hormone-Secreting Pituitary Adenoma; Humans; Hyperplasia; Immunohistochemistry; Male; Microscopy, Immunoelectron; Middle Aged; Neuropeptide Y; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Receptors, Neuropeptide Y; RNA, Messenger; Young Adult

Neuropeptide Y (NPY) exerts its functions through six subtypes of receptors (Y₁-Y₆). Biliary homeostasis is regulated by several factors through autocrine/paracrine signaling. NPY inhibits cholangiocarcinoma growth; however, no information exists regarding the autocrine/paracrine role of NPY on biliary hyperplasia during cholestasis. The aims of this study were to determine: 1) the expression of NPY and Y₁-Y₅ in cholangiocytes and 2) the paracrine/autocrine effects of NPY on cholangiocyte proliferation. Normal or bile duct ligation (BDL) rats were treated with NPY, neutralizing anti-NPY antibody, or vehicle for 7 days. NPY and NPY receptor (NPYR) expression was assessed in liver sections and isolated cholangiocytes. NPY secretion was assessed in serum and bile from normal and BDL rats, as well as supernatants from normal and BDL cholangiocytes and normal rat cholangiocyte cell line [intrahepatic normal cholangiocyte culture (NRICC)]. We evaluated intrahepatic bile ductal mass (IBDM) in liver sections and proliferation in cholangiocytes. With the use of NRICC, the effects of NPY or anti-NPY antibody on cholangiocyte proliferation were determined. The expression of NPY and all NPYR were increased after BDL. NPY levels were lower in serum and cholangiocyte supernatant from BDL compared with normal rats. NPY secretion from NRICC was detected at both the basolateral and apical domains. Chronic NPY treatment decreased proliferating cellular nuclear antigen (PCNA) expression and IBDM in BDL rats. Administration of anti-NPY antibody to BDL rats increased cholangiocyte proliferation and IBDM. NPY treatment of NRICC decreased PCNA expression and increased the cell cycle arrest, whereas treatment with anti-NPY antibody increased proliferation. Therapies targeting NPY-mediated signaling may prove beneficial for the treatment of cholangiopathies.

Topics: Animals; Antibodies, Neutralizing; Autocrine Communication; Bile Ducts, Intrahepatic; Cell Line; Cell Proliferation; Cholestasis; Homeostasis; Hyperplasia; Male; Neuropeptide Y; Paracrine Communication; Proliferating Cell Nuclear Antigen; Rats; Rats, Inbred F344; Receptors, Neuropeptide Y; RNA, Messenger; Signal Transduction

Interstitial white matter neurons (IWMNs) may reflect immature neurons that migrate tangentially to the neocortex from the ganglionic eminence to form cortical interneurons. Alterations of interneuron markers have been detected in gray matter of dorsolateral prefrontal cortex in schizophrenia, and IWMNs are also reported to be altered in schizophrenia. In this study, we considered whether a potential link exists between these two pathological findings.. From a cohort of 29 schizophrenia subjects and 37 control subjects, IWMN densities were determined in the dorsolateral prefrontal cortex by counting neuronal nuclear antigen (NeuN) and somatostatin (SST)-positive cells. Double-label immunofluorescence was carried out to determine the overlap between SST+/NeuN+ and SST+/neuropeptide Y + neurons.. We found that density of NeuN + IWMNs in superficial white matter is significantly increased in schizophrenia subjects compared with control subjects. There was a significant negative correlation between SST mRNA expression in gray matter and NeuN + IWMN density. In schizophrenic patients with increased NeuN IWMN density, the density of SST-expressing neurons in white matter was also higher compared with control subjects. A subpopulation of SST immunopositive cells also show coexpression of neuropeptide Y.. Our study confirmed previous results indicating that the density of NeuN + IWMNs is increased in superficial white matter in schizophrenia. We provide the first evidence that increased IWMN density correlates with a gray matter interneuron deficit, suggesting that migration of interneurons from white matter to the cortex may be deficient in some patients with schizophrenia, consistent with an interneuron deficit in schizophrenia.

Topics: Antigens, Nuclear; Cerebrum; Female; Humans; Hyperplasia; Interneurons; Male; Middle Aged; Nerve Fibers, Myelinated; Nerve Tissue Proteins; Neuropeptide Y; Prefrontal Cortex; Schizophrenia; Somatostatin

The innervation of the human adrenal gland and of cortical lesions was studied in sections of cortical tissue (n=10), hyperplastic cortical tissue (n=3), and tissue from cortical adenomas (n=5) and carcinomas (n=6). The presence and distribution of nerve structures containing neuronal markers indicating sympathetic and parasympathetic innervation were studied by immunohistochemistry and the co-existence and co-localization patterns of the different markers by immunofluorescence. The cortex and hyperplastic cortical tissue had a moderate to rich supply of nerve structures containing the typical neuronal markers: protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), small vesicle synaptic protein type 2 (SV2), and nerves showing immunoreactivity to the adrenergic marker tyrosine hydroxylase (TH). All these immunoreactive nerves were located predominantly adjacent to blood vessels, but also among parenchymal cells. The cortex showed numerous nerve structures containing the neuropeptide substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal protein (VIP), but few nerves containing these peptides were seen in hyperplastic cortical tissue. Typical markers were occasionally observed in cortical adenomas but were not found in carcinomas, except in a few cases where PGP 9.5 and NSE were present, but only adjacent to necrotic areas. Nerves containing NPY and VIP occurred in varying numbers in both adenomas and carcinomas. NPY- and VIP-immunoreactive nerve structures were seen mostly alongside blood vessels. There were several types of co-existence. For instance, NSE/VIP-, TH/VIP- and TH/NPY-immunoreactive nerve structures were often seen in the same trunk, but were only partly co-localized.

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Carcinoma; Fluorescent Antibody Technique, Indirect; Humans; Hyperplasia; Immunoenzyme Techniques; Membrane Glycoproteins; Nerve Tissue Proteins; Neuropeptide Y; Parasympathetic Nervous System; Phosphopyruvate Hydratase; Sympathetic Nervous System; Thiolester Hydrolases; Tyrosine 3-Monooxygenase; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Neuropeptide Y (NPY) gene is expressed in human pituitary gland where its function is partially elucidated. NPY could act as a neuroendocrine modulator within this gland. This study was undertaken to assess whether NPY expression is correlated to various pathological situations. Using a highly specific anti-NPY monoclonal antibody, immunohistochemistry analysis was performed in surgically removed pituitary glands. The study included biopsies from 112 human pituitary adenomas, 12 hyperplastic glands and normal anterior pituitary tissues in 34 cases. NPY is immunodetected in 33% of all adenomas, 25% hyperplastic glands and 12% of non-tumoral pituitary gland. NPY expression was significantly higher in adenomas compared to the normal gland. However, no correlation was observed between NPY content and the type of hormonal secretion, sex, age and the status of tumour proliferating potential.

Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Child; Child, Preschool; Female; Gonadotropins, Pituitary; Human Growth Hormone; Humans; Hyperplasia; Immunohistochemistry; Infant; Male; Middle Aged; Neuropeptide Y; Pituitary Gland, Anterior; Pituitary Neoplasms

Hyperplasia of vascular smooth muscle cells (VSMCs) occurs during HIV infection, part of a spectrum of HIV-mediated cardiovascular and microvascular pathologies. These changes are not due to direct viral infection but may involve the receptor-mediated action of viral proteins, such as the envelope protein gp120. We sought to identify gp120 receptors which might mediate the vascular smooth muscle cell hyperplasia present in HIV infection. A homology between neuropeptide Y (NPY) and the previously identified receptor-active V2-region of gp120 defined by an octapeptide sequence (Peptide T) related to VIP was noted. Since NPY is mitogenic for VSMCs we therefore determined whether gp120 shares this activity. Rat aortic VSMCs were treated for 24 h with human (h)NPY and gp120 in the presence of 0.5% serum to measure [3H]thymidine incorporation, an index of cell proliferation. NPY increased [3H]thymidine incorporation by 80% after a 24-h treatment in a bimodal fashion, with peak effects at 10(-10) M and 10(-8) M. Gp120 was an even more potent mitogen for VSMCs with peak activity occurring at 10(-12) M. Peptide T was equipotent with gp120, and slightly less efficacious, suggesting that this domain may mediate gp120 effects on VSMCs. When combined, gp120 and NPY acted to antagonize one another, lowering DNA synthesis to basal levels. The profile of pharmacologic inhibition supports a role for NPY receptors since antagonists of Y1 and Y2 subtypes substantially or completely inhibited gp120-mediated VSMC proliferation. This is the first demonstration of the proliferative effects of HIV viral protein gp120 on VSMCs. The effect appears to be mediated via gp120 sequences related to VIP, peptide T, and NPY. These ligands may be competitive inhibitors of binding or gp120 processing. Novel treatments may emerge based upon VIP and NPY receptor antagonists if further work substantiates a role for gp120 in the vascular abnormalities of AIDS.

Topics: Amino Acid Sequence; Animals; Cardiovascular Diseases; Cell Division; Cells, Cultured; HIV; HIV Envelope Protein gp120; HIV Infections; Humans; Hyperplasia; Mitogens; Molecular Sequence Data; Muscle, Smooth, Vascular; Neuropeptide Y; Peptide T; Rats; Receptors, Neuropeptide Y; Sequence Homology, Amino Acid; Vasoactive Intestinal Peptide

Neuropeptide Y (NPY) is a 36 amino acid peptide known to inhibit glucose-stimulated insulin secretion. NPY has recently been shown to be synthetized within rat islets of Langerhans and to be secreted in a differentiated rat insulin-secreting cell line, and as to this date the localization of NPY in human endocrine pancreas has not been reported. As NPY shares high amino acid sequence homology with peptide YY (PYY) and pancreatic polypeptide (PP), the polyclonal antibodies raised against these peptides often cross-react with each other. To demonstrate the presence of NPY in the human endocrine pancreas, we used a highly specific monoclonal antibody raised against NPY and another against its C-flanking peptide (CPON). We studied three cases of hyperplasia of Langerhans islets and 11 cases of endocrine tumors of the pancreas. NPY and CPON were detected in all three cases of hyperplasia. For the 11 pancreatic tumors, five and nine of the tumors were positive for the antibodies NPY and CPON, respectively. The two negative tumors for CPON immunoreactivity were differentiated insulinomas, which showed no evidence of other hormonal secretion. In normal Langerhans islet, NPY and CPON immunoreactivities were colocalized in glucagon-producing cells (alpha-cells) and in a few insulin-secreting cell (beta-cells).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Animals; Antibodies; Carcinoid Tumor; Carcinoma; Cell Line; Female; Humans; Hyperplasia; Immunohistochemistry; Insulin; Insulinoma; Islets of Langerhans; Male; Middle Aged; Neuroendocrine Tumors; Neuropeptide Y; Pancreatic Hormones; Pancreatic Neoplasms; Rats