Endocrine Abstracts

The beneficial effects of relaxin peptide treatment have been demonstrated in animal models of liver fibrosis. However, the low stability of peptide in vivo prevents using it in chronic treatments. We have identified a series of small molecule allosteric agonists of the human relaxin receptor, RXFP1. The therapeutic effects of lead compound ML290 was tested in various models of liver fibrosis. To analyze the anti-fibrotic effects of ML290 on gene expression, we used p...

Epidemiological studies have shown that caffeine increases plasma SHBG levels and also reduce the risk of type 2 diabetes. There are no reports describing any molecular mechanism by which caffeine regulates hepatic SHBG production. The aim of the present study was to explore whether caffeine regulates SHBG production and to determine the associated molecular mechanisms. For this purpose, in vitro and in vivo studies were performed using human HepG2 cells and ...

Previously, we reported that aphidicolin acutely increases nitric oxide (NO) production in bovine aortic endothelial cells (BAECs) by increasing phosphorylation of endothelial nitric oxide synthase at serine 1179 (p-eNOS-Ser1179) and decreasing phosphorylation at serine 116 (p-eNOS-Ser116) without altering eNOS protein expression. Here, we demonstrate that prolonged treatment with aphidicolin (over 24 h) also increased NO production in BAECs. Unlike the a...

Objectives: Despite the introduction of new molecular targeted therapies, there is still an unmet need for an effective systemic therapy for advanced medullary thyroid carcinoma (MTC). As MTC expresses cholecystokinine-2 (CCK-2) receptors at a high incidence and density, targeting the CCK-2 receptor with radiolabelled gastrin analogues is a potential approach for radionuclide therapy. Unfortunately, kidney and bone marrow toxicity precluded therapeutic applications of CCK-2 re...

Introduction: The treatment of choice for parathyroid carcinoma (PC) is a radical en bloc resection. Treatment options for patients with metastatic PC are limited especially if a complete tumor removal cannot be performed. We present four cases of PC patients with multiple metastasis and refractory hypercalcemia that eventually received a multikinase inhibitor with different response on therapy.Clinical cases: The first patient was a 27-year-old woman wi...

Even though serine-threonine kinase PAK1 is activated by estrogen and plays an important role in breast cancer, the role of PAK1 in estrogen response is not fully understood. We have shown that estrogen activates PAK1 through both ERα and GPER1 plasma membrane receptors and that cytoplasmic Etk/Bmx directly phosphorylates Tyr153-PAK1 and activates PAK1 in response to estrogen. We have described a signaling complex composed of pTyr-PAK1, Etk, the heterotrimeric G-protein s...

Beta cell senescence is being regarded as the one of the mechanisms of beta cell dysfunction. Melatonin secreted primarily from the pineal glandregulates a variety of physiological functions, such as sleep, circadian rhythms, and neuroendocrine actions. Melatonin has also very strong anti-oxidant effects. The effects of melatonin on the pancreatic beta cell senescence induced by glucolipotoxicity have not been studied. INS-1 cells were exposed to 33mM glucose with palmitate 20...

Introduction: Environmental pollutants especially those endowed with endocrine disrupting activities have been shown to contribute to metabolic related diseases suggesting that hormonal deficit conditions as observed in post-menopausal women may constitute aggravating conditions. To explore this hypothesis, we used the model developed in the laboratory which consists in a chronically exposure of mice to low-dosed chemicals in mixture incorporated in a high-fat-high-sucrose die...

Bisphenol A (BPA) is a widely used chemical and belongs to the list of metabolism-disrupting chemicals. BPA is banned in several countries and replaced by others BPA-analogs. We investigate the effects of BPA and 6 BPA-analogs (BPS, BPAF, BPF, BPB and BADGE) on the response of the human melanocortin 4 receptor (MC4R), a receptor involved in food intake and weight control, to its natural ligands. We used HEK293 cells line transiently transfected with human MC4R to determine the...

Introduction: The impairment of liver function and enhancement for NAFLD development may be attributed to the ubiquitous exposure to endocrine disrupting chemicals such as phthalates. In this study the urinary levels of monoethyl phthalate (MEP) and mono-(2-ethylhexyl) phthalate (MEHP) were compared with the parameters of hepatic function and lipids in overweight, diabetic patients and normal weight population.Methods and patients: In 305 volunteers of b...