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TSH-induced cAMP accumulation in cells obtained from normal and pathological thyroid tissue was studied during the first 12 days of primary culture. In normal thyroid tissue cultures (N = 7), the response of cAMP to TSH was present from the second day of culture and reached its maximum after 8 days. A similar behaviour was observed in cultures obtained from euthyroid sporadic goitres (N = 8), even if the rate of response was slightly lower than that of normal tissue. Similarly, cultured cells from euthyroid 'autonomous' nodules (N = 8) appeared to be responsive to TSH during the period of study, but the rate of response was also lower than in the controls. On the contrary, in cultures obtained from toxic adenomas (N = 5) and from diffuse toxic goitres (N = 5) the response to TSH was absent during the first 4 days of culture. The cells became sensitive to TSH from 6 and 6 day onwards, with the rate of response increasing progressively and reaching its maximum on day 12. Finally, in cultured cells obtained from different areas of multinodular toxic goitres (N = 4), the response to TSH was similar to that of euthyroid goitres in cells prepared from 'cold' areas, and to that of toxic adenomas in cells obtained from 'hot' areas. The present data demonstrate the existence of an inhibitory action of unknown factors, possibly iodothyronines or thyroglobulin, on the TSH effect in short-term cultures obtained from thyrotoxic tissues. A normal TSH responsiveness can be restored when the culture is prolonged. 相似文献
95.
P Vitti C M Rotella W A Valente J Cohen S M Aloj P Laccetti F S Ambesi-Impiombato E F Grollman A Pinchera R Toccafondi L D Kohn 《The Journal of clinical endocrinology and metabolism》1983,57(4):782-791
Immunoglobulin G (IgG) preparations derived from the sera of patients with hyperthyroidism due to Graves' disease (TSAb) as well as a monoclonal IgG derived from heterohybridoma fusions of Graves' lymphocytes augmented cAMP levels in a continuous strain of functioning rat thyroid cells (clone FRTL-5) in culture. Optimal stimulation was the same for both types of IgG preparations when measured after 2 h of incubation with 5 X 10(4) cells/well and using cells maintained in a nongrowth, TSH-deficient medium for 7 days. At low IgG concentrations, the stimulatory activities of both preparations exhibited a linear dependence on concentration and similar Ka values (approximately 4 X 10(-8) M) despite the fact that 65% of the Graves' serum IgG preparations had a significantly better ability to inhibit TSH binding to membrane preparations. The Ka value for TSH in the same assay was about 5 X 10(-12) M. Using this cell assay, 90% of a series of hyperthyroid Graves' IgG preparations exhibited stimulating activity, a value comparable to the frequency of positive results found by ourselves and others using human thyroid cell and slice systems. In contrast, only 10% of patients who were euthyroid 1 yr after antithyroid drug withdrawal (n = 21) exhibited stimulating activity, and no stimulating activity was detected in patients with nontoxic nodular goiter (n = 11), toxic adenoma (n = 5), or thyroid carcinoma (n = 6). The studies suggest that an optimized rat FRTL-5 thyroid cell system is a clinically useful and convenient alternative to human thyroid cell and slice systems for detecting TSAbs. 相似文献
96.
Insulin-like growth factor-I: autocrine secretion by human thyroid follicular cells in primary culture 总被引:6,自引:0,他引:6
B Tode M Serio C M Rotella G Galli F Franceschelli A Tanini R Toccafondi 《The Journal of clinical endocrinology and metabolism》1989,69(3):639-647
Insulin-like growth factor-I (IGF-I) stimulates the growth of thyroid cells of different animal species. However, conflicting results have been reported as regards the function and mechanism of the action of IGF-I at the thyroid level. This study was designed to determine whether normal human thyroid cells have IGF-I receptors and whether IGF-I could act on such cells through an autocrine mechanism. Human thyroid follicular cells in primary culture, not contaminated by fibroblasts, were used. They had specific and saturable binding sites for IGF-I, as revealed by radiolabeled binding method, and displayed an average receptor number of 2000/cell. Under the same experimental conditions, insulin receptors were not detectable. Human thyroid follicular cells secreted IGF-I into the culture medium, as assessed by a specific chemiluminescent immunoassay. The IGF-I secretory process was detectable for at least 12 days of culture, but a high degree of variability has been found among individual samples. Acid-gel chromatography demonstrated that IGF-I and a higher mol wt IGF-I, most likely IGF-I bound to its binding protein, were secreted by human thyroid cells. TSH stimulated the secretion of the two molecules in normal human thyroid cells. The TSH effect on IGF-I secretion was concentration dependent between 0.1 nmol/L and 0.1 mumol/L. GH stimulated IGF-I synthesis by thyroid cells in a concentration range from 20-200 micrograms/mL. Since binding studies demonstrated the presence of IGF-I receptors on human thyroid cells, IGF-I probably regulates human thyroid function through an autocrine mechanism. 相似文献
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98.
Glucagon-like peptide 1 (GLP-1) and metabolic diseases 总被引:3,自引:0,他引:3
Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone, mainly secreted after meals, which enhances glucose-induced insulin secretion and induces satiety. It has been reported that GLP-1 levels after a mixed meal and after an oral glucose load are reduced in patients with Type 2 diabetes. The reduction of oral glucose-stimulated active GLP-1 levels in patients with Type 2 diabetes has also been observed during euglycemic iperinsulinemic clamp. The reduction of post-prandial circulating active GLP-1 in Type 2 diabetic subjects, as a consequence of chronic hyperglycemia, could contribute to the reduction of early post-prandial insulin secretion; in fact, the administration of GLP-1 receptor antagonists to healthy volunteers elicits both an impairment of meal-induced insulin secretion and an increase of post-prandial glycemia similar to that observed in Type 2 diabetes. GLP-1 is rapidly inactivated by dipeptidyl peptidase IV (DPP-IV), an enzyme produced by endothelial cells in different districts and that circulates in plasma. It is still not clear whether the reduction of mealor oral-glucose stimulated GLP-1 levels in Type 2 diabetic patients is due to impairment of secretion, increase of degradation, or both. The major limitation of using GLP-1 to treat diabetic patients is the short half-life of the native compound. There are now several compounds in various stages of pre-clinical or clinical development for the treatment of Type 2 diabetes that utilize the GLP-1 signaling pathway; these include GLP-1 receptor agonists with extended half-lives, and inhibitors of DPP-IV that increase circulating levels of endogenous, intact and bioactive GLP-1. 相似文献
99.
We investigated whether two alternative HOMA-IR thresholds recently proposed identify similar phenotype and have the same impact on gluco-metabolic risk. The two IR cutoffs, IR1 and IR2 (IR1: HOMA-IR >5.9 and IR2: HOMA-IR between 2.8 and 5.9 with HDL-C <51 mg/dl), were applied to a database of 2,360 outpatients, and their association with phenotypes, glucose tolerance, lipids and metabolic syndrome (MetS) was examined. IR1 group showed 5.5 % of overweight versus 27.8 % of IR2 subjects, and obesity was present in 92.3 versus 68.4 %, respectively. We observed the major prevalence of pathological waist in IR1 compared to IR2 subjects: 96.0 versus 80.5 % (p < 0.001). After OGTT, IR1 patients presented higher prevalence of impaired glucose tolerance (IGT: 25.8 vs. 20.2 %, p < 0.001) and DM2 was diagnosed in 39.7 % of IR1 versus 11.3 % of IR2 patients (p < 0.001) with odds ratio (OR) 8.3 (95 % CI 6.1–11.6) versus 0.8 (0.6–1.2), respectively. IR1 versus IR2 cutpoint showed higher significant (mean ± SEM) total cholesterol (224.8 ± 2.6 vs. 213.1 ± 1.7 mg/dl, p < 0.001) and triglyceride (208.1 ± 12.3 vs. 177.4 ± 4.8 mg/dl, p < 0.001) levels. MetS prevalence was significantly higher in IR1 than IR2 (89.0 vs. 78.3 %, p < 0.001). The IR1 cutpoint was associated with a higher OR of MetS 7.3 (5.3–10.2) versus 5.2 (2.8–9.5) of IR2. In summary, the two alternative HOMA-IR cutoffs identify subjects with different distribution of phenotypes and gluco-metabolic risk. The IR1 patients are characterized by higher prevalence of obesity, pathological waist, MetS, dyslipidemia and IGT/DM2. 相似文献
100.