neuropeptide-y and Adenoma

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

The aim of this study was to assess human intracranial tumours for their gene expression pattern of the vasoactive peptide adrenomedullin (AM), its receptor (AM-R) and leptin, which exerts multiple biological effects including proliferation and angiogenesis via the leptin receptor (OB-Rb). Gene activity of neuropeptide Y (NPY) was monitored additionally. We investigated whether there was a characteristic gene expression pattern of AM and leptin in different intracranial tumours, depending on their proliferation activity and biological behaviour. We investigated 35 non-functioning pituitary adenomas (including eight null cell, four silent plurihormonal, 23 silent gonadotroph adenomas), seven somatotropinomas, seven prolactinomas, eight meningiomas, five astrocytomas, two glioblastoma multiformes and unaffected temporal lobe (n = 8). Quantitative reverse transcriptase-polymerase chain reaction (TaqMan RT-PCR) was performed. AM mRNA was detectable in all tumour specimens. AM/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio was significantly higher in somatotropinomas, as was AM/CD31 ratio in prolactinomas, compared with inactive adenomas (P < 0.05). AM-R mRNA was found in all tumour subgroups in small quantities but, in general, higher in tumours than in temporal lobe tissue, respectively. AM-R/CD31 ratio was significantly higher in prolactinomas than in inactive adenomas (P < 0.05). Leptin was detectable in very low quantities in each subgroup. OB-Rb gene expression was found in all tumour subgroups, OB-Rb/GAPDH ratio was highest for meningiomas (P < 0.0001, compared with temporal lobe). NPY mRNA was detectable in temporal lobe in higher quantities than in tumours (P < 0.0001), and almost undetectable in prolactinomas and astrocytomas. Our data demonstrate that AM and AM-R, NPY, as well as leptin and OB-Rb, are expressed in various intracranial tumours in humans but their particular function has to be elucidated further. At present, there is no evidence for a cross-talk on transcriptional level between the peptidergic vasodilative system AM and the putative angiogenic and proliferation affecting factor leptin.

Topics: Adenoma; Adrenomedullin; Adult; Aged; Brain Neoplasms; Carrier Proteins; Female; Gene Expression; Hormones; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Peptides; Pituitary Neoplasms; Receptors, Adrenomedullin; Receptors, Cell Surface; Receptors, Leptin; Receptors, Peptide

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

Autonomic nerve fibers immunoreactive to Neuropeptide Y (ir-NPY) were counted in tissue samples from human thyroid glands. Samples were taken from the non-pathological parts of gland material removed surgically from nine female patients suffering from struma nodosa or solitary adenoma. The ir-NPY fiber population was subdivided into fibers associated with blood vessels (perivascular innervation) and fibers either attached to the wall epithelium of the follicles or coursing within the gland's connective tissue (extravascular innervation). Most perivascular fibers were found in arterioles (20-40 microns diam.). Capillaries (< 10 microns diam.) were not innervated. These fibers surrounded the vessels. They formed a characteristic reticular or coil-like pattern close to the tunica adventitia. Sometimes a second, smaller fiber layer was found between the tunica adventitia and media. Ir-NPY fibers were unmyelinated and less than 2 microns in diameter. Based on counts of the gland's arterial supply, it was calculated that about 23% of all arterial vessels (< 80 microns diameter) were innervated. On average, one innervated arteriole was found per 0.2 mm2 of thyroid tissue. Extravascular fibers were less frequent. In ca. 3 mm2 of thyroid tissue at least two ir-NPY fibers were found outside the vessels close to the follicular epithelium or within the connective tissue. No follicles with a dense ir-NPY innervation were found. Extravascular fibers were less arborized. They appear to be either smaller or less intensively stained than perivascular fibers, although some extravascular fibers were collaterals of the perivascular fibers.

Topics: Adenoma; Autonomic Nervous System; Female; Goiter, Nodular; Humans; Immunohistochemistry; Nerve Fibers; Neuropeptide Y; Thyroid Gland; Thyroid Neoplasms

Topics: Adenoma; Animals; Cats; Chickens; Humans; Nerve Fibers; Nerve Tissue Proteins; Neuropeptide Y; Neuropeptides; Neurotransmitter Agents; Parathyroid Glands; Parathyroid Neoplasms; Pituitary Adenylate Cyclase-Activating Polypeptide; Reference Values; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide