peptide-yy and Syndrome

Primary carcinoid tumors are rare neoplasms of the ovary. Of the 4 histologic subtypes, ovarian carcinoid tumors with insular patterns produce carcinoid syndrome in approximately one third of cases, versus strumal and trabecular carcinoids which very rarely cause typical carcinoid syndrome. A unique presentation of ovarian carcinoid tumors with concurrent severe constipation has been reported, which is thought to represent a new carcinoid syndrome. The proposed mechanism is the production of peptide YY by the tumor, a gastrointestinal hormone responsible for decreasing gut motility. We report a case of a 34-yr-old white woman who presented with constipation and weight loss for 1 yr, and was found to have a unilateral ovarian strumal carcinoid, which produced peptide YY as demonstrated by immunohistochemistry. The 13 previous case reports of ovarian carcinoids with constipation are reviewed and the clinicopathologic features are discussed. This report and literature review further solidifies this entity as a new type of carcinoid syndrome.

Topics: Adult; Carcinoid Tumor; Comorbidity; Constipation; Female; Gastrointestinal Motility; Humans; Ovarian Neoplasms; Ovariectomy; Ovary; Peptide YY; Severity of Illness Index; Struma Ovarii; Syndrome; Treatment Outcome

Hypothalamic neuropeptide Y (NPY) is implicated in the regulation of a variety of physiological functions, notably energy homeostasis and reproduction. Chronically elevated NPY levels in the hypothalamus, as in genetically obese ob/ob mice, are associated with obesity, a syndrome of type 2 diabetes, and infertility. However, it is not known which of the five cloned Y receptors mediate these effects. Here, we show that crossing the Y2 receptor knockout mouse (Y2(-/-)) onto the ob/ob background attenuates the increased adiposity, hyperinsulinemia, hyperglycemia, and increased hypothalamo-pituitary-adrenal (HPA) axis activity of ob/ob mice. Compared with lean controls, ob/ob mice had elevated expression of NPY and agouti-related protein (AgRP) mRNA in the arcuate nucleus and decreased expression of proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA. Y2 deletion in ob/ob mice significantly increased the hypothalamic POMC mRNA expression, with no effect on NPY, AgRP, or CART expression. [Y2(-/-)ob/ob] mice were no different from ob/ob littermates with respect to food intake and body weight, and Y2 receptor deficiency had no beneficial effect on the infertility or the reduced hypothalamo-pituitary-gonadotropic function of ob/ob mice. These data demonstrate that Y2 receptors mediate the obese type 2 diabetes phenotype of ob/ob mice, possibly via alterations in melanocortin tonus in the arcuate nucleus and/or effects on the HPA axis.

Topics: Adipose Tissue; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Female; Gene Deletion; Gonadotropins; Hypothalamo-Hypophyseal System; Insulin; Male; Mice; Mice, Knockout; Neuropeptides; Obesity; Peptide Fragments; Peptide YY; Pituitary-Adrenal System; Receptors, Neuropeptide Y; Syndrome; Thermogenesis; Thyrotropin

Neuropeptide Y (NPY) is involved in the central regulation of appetite, sexual behavior, and reproductive function. We have previously shown that chronic infusion of NPY into the lateral ventricle of normal rats produced an obesity syndrome characterized by hyperphagia, hyperinsulinism and collapse of reproductive function. We further demonstrated that acute inhibition of LH secretion in castrated rats was preferentially mediated by the NPY receptor subtype 5 (Y(5)). In the present study, the effects of chronic, central infusion of NPY, or the mixed Y2-Y5 agonist PYY(3-36), were evaluated both in normal male C57BL/6J mice and Sprague-Dawley rats. After a 7-day infusion to male mice, both NPY and PYY(3-36) at 5 nmol per day, induced marked hyperphagia leading to significant increases in body and fat pad weights. Furthermore, both compounds markedly reduced several markers of the reproductive axis. In the rat study, PYY(3-36) was more active than NPY to inhibit the pituitary-testicular axis, confirming the importance of the Y5 subtype for such effects. In the mouse, chronic NPY infusion induced a sustained increase in corticosterone and insulin secretion. Plasma leptin levels were also markedly increased possibly explaining the observed reduction in gene expression for hypothalamic NPY. Gene expression for hypothalamic POMC was reduced in the NPY- or PYY(3-36)-infused mice, suggesting that NPY exacerbated food intake by both acting through its own receptor(s), and reducing the satiety signal driven by the POMC-derived alpha-MSH. The present study in the mouse suggests in analogy with available rat data, that constant exposure to elevated NPY in the hypothalamic area unabatedly enhances food intake leading to an obesity syndrome including increased adiposity, insulin resistance, hypercorticism, and hypogonadism, reminiscent of the phenotype of the ob/ob mouse, that displays elevated hypothalamic NPY secondary to lack of leptin negative feedback action.

Topics: Animals; Hyperphagia; Hypogonadism; Insulin Resistance; Lateral Ventricles; Leptin; Male; Mice; Mice, Inbred C57BL; Neuropeptide Y; Obesity; Peptide Fragments; Peptide YY; Rats; Rats, Sprague-Dawley; Syndrome