1,720,988 research outputs found
Anatomy and physiology of the neuroendocrine system. Regulation of the neuroendocrine system: C-cell of the thyroid.
No full textThis chapter describes embryonic development, anatomy, calcitonin secretion regulation and function, Calcitonin-related peptide secretion and functio
Isolated R171Q amino acid change in MEN1 gene: polymorphism or mutation?
No full textWe suggest that the isolated R171Q amino acid change might be regarded as a point mutation with low penetrance MEN1 phenotype, rather than a harmless polymorphism. Therefore, MEN1 patients carrying this genetic alteration, as well as clinically unaffected carriers, should undergo a careful endocrine investigation and a close clinical and biochemical follow-up
Evidence for androgen receptor gene expression and growth effect of dihydrotestosterone on human adrenocortical cells.
No full textBlood growth hormone-binding protein levels in premenopausal and postmenopausal women: roles of body weight and estrogen levels
No full textABSTRACT
A substantial proportion of GH circulates bound to high affinity
GH-binding protein (GHBP), which corresponds to the extracellular
domain of the GH receptor. Current evidence indicates that nutritional
status has an important role in regulating plasma GHBP levels
in humans. In the present study the relationship among plasma
GHBP levels, body composition [by bioelectrical impedance analysis
(BIA) and dual energy x-ray absorptiometry (DEXA)] and serum estradiol
(E2) was evaluated in premenopausal (n 5 92) and postmenopausal
(n 5 118) healthy women with different body weight [three
groups according to body mass index (BMI): normal, 18.5–24.99; overweight,
25–29.99; obese, 30–39.99 kg/m2]. Plasma GHBP levels were
measured by high pressure liquid chromatography gel filtration. GH
and insulin-like growth factor I levels were determined by immunoradiometric
assay and RIA, respectively.
GHBP levels were significantly higher in premenopausal women
with BMI above 25 kg/m2 (overweight, 3.789 6 0.306 nmol/L; obese,
4.37260.431 nmol/L) than those observed in postmenopausal women
(overweight, 1.425 6 0.09 nmol/L; obese, 1.506 6 0.177 nmol/L). No
significant differences were found between normal weight premenopausal
(1.741 6 0.104 nmol/L) and postmenopausal (1.524 6 0.202
nmol/L) women. In premenopausal women GHBP levels correlated
positively with BMI (r 5 0.675; P , 0.001), fat mass (FM; r 5 0.782;
P , 0.001; by BIA; r 5 0.776; P , 0.001; by DEXA), truncal fat (TF;
r 5 0.682; P , 0.001), waist to hip circumference ratio (WHR; r 5
0.551; P , 0.001), and E2 (r 5 0.298; P , 0.05), whereas no significant
correlation was found in postmenopausal women between GHBP levels
and BMI, FM, TF, WHR, or E2. In normal weight pre- and postmenopausal
women GHBP levels did not change between the ages of
20 and 69 yr. No statistically significant correlation was found between
GHBP and age for all groups studied. Moreover, in two distinct
subgroups of pre- and postmenopausal women, aged 40–49 yr, the
direct relationship between GHBP levels and all indexes of adiposity
were only observed in premenopausal women [BMI: r 5 0.836; P ,
0.001; FM: r 5 0.745 (BIA) and r 5 0.832 (DEXA); P , 0.001; TF: r 5
0.782; P , 0.001; WHR: r 5 0.551; P , 0.05], but not in postmenopausal
women.
In conclusion, the present data indicate a strong direct correlation
between GHBP and body fat in premenopausal, but not in postmenopausal
women, whereas they failed to detect a relationship between
GHBP and age. Therefore, these results suggest that endogenous
estrogen status may be an important determinant of the changes in
GHBP levels in women with different body weights
SOMATOSTATIN INHIBITS A MEDULLARY THYROID CARCINOMA CELL LINE GROWTH BY ACTIVATING SHP-1
No full textTargeting protein kinase C by Enzastaurin restrains proliferation and secretion in human pancreatic endocrine tumors.
No full textAbstract
Dysregulation of the protein kinase C (PKC) signaling pathway has been implicated in tumor progression. In this study, we investigate the effects of a PKC inhibitor, Enzastaurin, in human pancreatic neuroendocrine neoplasms (PNN) primary cultures and in the human pancreatic endocrine cancer cell line, BON1. To this aim six human PNN dispersed in primary cultures and BON1 cells were treated without or with 1-10 μM Enzastaurin and/or 100 nM IGF1 in the presence or absence of serum. Cell viability and apoptosis were evaluated after 48-72 h; Chromogranin A (CgA) and/or insulin secretion was assessed after 6 h of incubation. PKC expression was investigated by immunofluorescence and western blot. We found that Enzastaurin significantly reduced human PNN primary culture cell viability, as well as CgA and insulin secretion. Moreover, in the BON1 cell line Enzastaurin inhibited cell proliferation at 5 and 10 μM by inducing caspase-mediated apoptosis, and reduced phosphorylation of glycogen synthetase kinase 3β (GSK3β) and of Akt, both downstream targets of PKC pathway and pharmacodynamic markers for Enzastaurin. In addition, Enzastaurin blocked the stimulatory effect of IGF1 on cell proliferation, and reduced CgA expression and secretion in BON1 cells. Two different PKC isoforms are expressed at different levels and have partially different subcellular localization in BON1 cells. In conclusion, Enzastaurin reduces cell proliferation by inducing apoptosis, with a mechanism likely involving GSK3β signaling, and inhibits secretory activity in PNN in vitro models, suggesting that Enzastaurin might represent a possible medical treatment of human PNN
Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism.
No full textSynthesis and biological activity of carboxyl terminally extended ermorphins
No full textDermorphinoyl(DMR)-glycine, DMR-sarcosine and DMR-glycyl-arginine have been prepared in order to examine the effect of C-terminal extension of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) on opioid activity. On GPI preparation the addition of Gly, Sar, or Gly-Arg to the carboxyl terminus of dermorphinoic acid was detrimental to mu activity: dermorphinoyl-derivatives, in fact, retain only 5-20% of dermorphin potency. Following intracerebroventricular administration (tail-flick test), whereas the analgesic activities of compounds showed the trend dermorphin greater than DMR-Sar greater than DMR-Gly-Arg greater than DMR-Gly greater than morphine, the nonapeptide displayed highest activity after subcutaneous injection in mice: DMR-Gly-Arg was 2.5 and 10 times more potent than dermorphin and morphine, respectively
Everolimus as a new potential antiproliferative agent in aggressive human bronchial carcinoids
No full textBronchial carcinoids (BCs) are rare tumors originating from endocrine cells dispersed in the respiratory epithelium. It has been previously demonstrated that everolimus, or RAD001, an mTOR inhibitor, has potent antiproliferative effects in human endocrine tumors. Our aim was to evaluate the possible antiproliferative effects of everolimus in human BCs in primary culture. We collected 24 BCs that were dispersed in primary cultures, treated without or with 1 nM-1 muM everolimus, 10 nM SOM230 (pasireotide, a somatostatin receptor multiligand), and/or 50 nM IGF1. Cell viability was evaluated after 48 h, and chromogranin A (CgA) as well as vascular endothelial growth factor (VEGF) secretion was assessed after 8 h incubation. Somatostatin receptors, mTOR, and AKT expression were investigated by quantitative PCR. We found that in 15 cultures (67.5%), everolimus significantly reduced cell viability (by approximately 30%; P<0.05 versus control), inhibited p70S6K activity (-30%), and blocked IGF1 proliferative effects. Everolimus also significantly reduced CgA (by approximately 20%) and VEGF (by approximately 15%) secretion. Cotreatment with SOM230 did not exert additive effects on cell viability and secretory activity. AKT expression was similar in responder and nonresponder tissues, while mTOR expression was significantly higher in the responder group, which was characterized by higher CgA plasma levels and bigger tumors with higher mitotic index and angiogenesis. Our data demonstrate that everolimus reduces VEGF secretion and cell viability in BCs with a mechanism likely involving IGF1 signaling, suggesting that it might represent a possible medical treatment for BCs
Hypopituitarism findings in patients with primary brain tumors 1 year after neurosurgical treatment: preliminary report
No full textI. F. 1.46
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