Role of endothelin-1 in the migration of human olfactory gonadotropin-releasing hormone-secreting neuroblasts

FNC-B4 neuroblasts that express both neuronal and olfactory markers have been established and cloned. These cells express GnRH and both the endothelin-1 (ET-1) gene and protein and respond in a migratory manner to GnRH in a dose-dependent manner. Previous research has shown that FNC-B4 cells produce and respond to ET-1 by regulating the secretion of GnRH through endothelin type A receptors and by stimulating their proliferation through endothelin type B (ETB) receptors. In this study, we found that FNC-B4 cells are able to migrate in response to ET-1 through the involvement of ETB receptors. Combined immunohistochemical and biochemical analyses showed that ET-1 triggered actin cytoskeletal remodeling and a dose-dependent increase in migration (up to 6-fold). Whereas the ETB receptor antagonist (B-BQ788) blunted the ET-1-induced effects, the ETA receptor antagonist (A-BQ123) did not. Moreover, we observed that FNC-B4 cells were independently and selectively stimulated by ET-1 and GnRH. We suggest that ET-1, through ETB receptor activation, may be required to maintain an adequate proliferative stem cell pool in the developing olfactory epithelium and the subsequent commitment to GnRH neuronal migratory pattern. The coordinate interaction between ET receptors and GnRH receptor participates in the fully expressed GnRH-secreting neuron phenotype

Current evidence for and against the TSH receptor being the common antigen in Graves' disease and thyroid associated ophthalmopathy

Journal ArticleResearch Support, Non-U.S. Gov'tReviewFLWINinfo:eu-repo/semantics/publishe

Clinical phenotype and beta-cell autoimmunity in Italian patients with adult-onset diabetes.

Objective: To characterize the phenotype of a large population of Italian patients with adult onset (2:40 years) diabetes who were attending outpatient clinics and who were screened for glutamic acid decarboxylase 65 autoantibodies (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and IA-2 beta/phogrin (IA-2 beta A). Design and Methods: This was a cross-sectional study comprising a total of 881 patients, aged :S 70 years. diagnosed with type 2 diabetes after the age of 40 years. and consecutively recruited in five clinics located in different geographic areas of Italy (Milan, Florence, Rome, Naples and Catania). Their mean disease duration was 8.1 (6.9: S.D.) years. GADA. IA-2A and IA-2 beta A were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2 beta. Anthropometric and clinical data were collected and compared amongst patients with or Without autoantibodies. Results: Sixty-three (7.1%) patients had one or more autoantibodies, 58 (6.6%) had GADA, 22 (2.5%) had IA-2A, six (0.7%) had IA-2 beta A and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2 beta A. in the absence of GADA. were found in only five patients. Autoantibody-positive patients were more often female (63.5 vs 36.5%; P 10 units vs 42.0% in those with <= 10 units: P < 0.007). Conclusions: Patients with adult onset diabetes characterized by autoimmunity to beta-cells showed a clinical phenotype with anthropometric features that differed from those classically observed in patients with type 2 diabetes. The number and titre of autoantibodies, which reflect the severity of autoimmunity and beta-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings