neuropeptide-y and Thyroid-Neoplasms

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; DNA, Neoplasm; Humans; Immunoenzyme Techniques; In Situ Hybridization; Neuropeptide Y; Neuropeptides; RNA, Messenger; Somatostatin; Thyroid Neoplasms; Tumor Cells, Cultured

Somatostatin modulates several renal tubular cell functions, including gluconeogenesis and proliferation. In this study, we demonstrate that cultured human proximal tubular epithelial cells (PTEC) express somatostatin. We also demonstrate positive and negative regulation of PTEC somatostatin production. We found that PTEC derived from 14 different human donors consistently expressed somatostatin mRNA and/or peptide as detected by RT-PCR and enzyme-linked immunoassay. Furthermore, Northern blot analysis revealed that PTEC express the same size mRNA transcript (750 nucleotides) as human thyroid carcinoma (TT) cells. The PTEC mitogens, epidermal growth factor(EGF) and hydrocortisone, inhibit PTEC somatostatin secretion, whereas forskolin (a direct stimulator of adenylate cyclase) and fetal bovine serum stimulate secretion. These findings raise the possibility that renal-derived somatostatin modulates tubular cell function in an autocrine/paracrine manner. Manipulation of this pathway may lead to novel methods with which to alter tubular cell proliferation and function in vivo.

Topics: Blotting, Northern; Cells, Cultured; Culture Media, Conditioned; Epithelial Cells; Humans; Kidney Tubules, Proximal; Neoplasm Proteins; Neuropeptide Y; Polymerase Chain Reaction; Protein Biosynthesis; RNA, Messenger; Somatostatin; Thyroid Neoplasms; Vasoactive Intestinal Peptide

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

An increasing number of regulatory peptides not coded by the calcitonin genes are known to occur in the thyroid C cells. We have now carried out light and electron microscopic immunocytochemical analyses on specimens of normal human thyroids and medullary carcinomas to establish the occurrence of members of the PP-PYY-NPY family in the C cell system. By means of site-directed immunocytochemistry we provide the first evidence that a molecule closely related to proNPY is present in normal and pathologic C cells, and is co-stored with calcitonin in the cytoplasmic dense-core granules. Preliminary observations also suggest that high levels of expression of NPY-gene products help to define a subset of tumours with a less aggressive behaviour.

Topics: Calcitonin; Humans; Immunohistochemistry; Neuropeptide Y; Pancreatic Polypeptide; Peptide YY; Peptides; Thyroid Gland; Thyroid Neoplasms

High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal less than 3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak = 1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50-fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.

Topics: Adrenal Gland Neoplasms; Epinephrine; Female; Humans; Middle Aged; Multiple Endocrine Neoplasia; Neuropeptide Y; Norepinephrine; Pheochromocytoma; Thyroid Neoplasms