Endocrine Abstracts

Tight junctions (TJ) exist as macromolecular complexes comprised of several types of membrane proteins, cytoskeletal proteins and signaling molecules. Recently, it has been observed that some components are regulated during epithelial–mesenchymal transition in cancer cells; however, the effects of estradiol (E2) have been poorly studied. This study sought to determine the role of E2 on the expression and cell localization of the TJ-associated protein...

TLR4 activation and the induction of endoplasmic reticulum stress (ERS) are two of the most important mechanisms connecting excessive dietary fat with insulin resistance. TLR4 activation is a primary event in the induction of cellular stress that contributes to increased inflammatory gene expression in metabolic diseases. However, the mechanisms linking these molecular events are unknown. The chaperones GRP78 and GRP94 play an important role during the assembly of newly transl...

We have previously shown that in pancreatic ductal epithelial cells, the expression of the water channel aquaporin-1 is under the control of the oxysterol receptor liver X receptor β. The aim of the present study was to investigate water balance in mice lacking each LXR isoform.Given free access to water, LXRβ−/− mice demonstrated an abnormal daily excretion of highly diluted urine, polyuria, with increased water intake compared to ...

Introduction: Prolactin (PRL) is a hormone utilized at both endocrine and autocrine levels. PRL regulates cyclin D1 expression through JAK2-mediated transcriptional activation of cyclin D1 promoter. Serine–threonine kinase PAK1 is also implicated in regulation of cyclin D1 gene expression. We previously showed that PAK1 binds to and is Tyr phosphorylated by JAK2. Herein we linked PRL and PAK1 as JAK2 substrate to stimulation of cyclin D1 promoter activity.<p class="ab...

One in 11 women develop breast cancer before the age of 75, and mortality is significant. Estrogens and progesterone (PROG) are mediators of breast cancer aetiology and progression, and are targets for both diagnostics and therapy. The actions of estrogens via estrogen receptor alpha (ERα) have been extensively studied, but the genomic actions of PROG via the progesterone receptor (PGR) are still not fully understood. This study investigates the genomic actions of PGR in ...

The estrogen receptor (ER) plays an important role in breast cancer development and progression. Hypoxia was shown to modulate the level of ERα expression and induce ligand-independent transcriptional activation of ERα, which may be intimately associated with the biology of breast carcinomas. Given that phosphorylation affects the transcriptional activity and stabilization of ERα, we examined the changes in phosphorylation of ERα under hypoxic conditions. H...

The Liver X Receptor (LXR) agonists have been shown to influence the development of hyperlipidemia and atherosclerosis in mouse models. It has also been demonstrated that some LXR agonists can cause hepatic steatosis in experimental animals. GH is also known to regulate hepatic metabolism and absence of the hepatic GH receptors leads to hepatic steatosis. In this study we analyzed whether actions of LXR agonists could involve interference with GH signaling. We showed that LXR ...

The thyroid hormone receptor (TR) belongs to a family of transcription factors which activity is modulated by the presence or absence of their particular ligand. Additionally, the transcriptional activity of TR is modulated by post-translational modifications such as phosphorylation, acetylation or ubiquitination. Here, I investigate whether TR might also be regulated by sumoylation. Sumoylation of transcription factors at defined lysine residues often leads to an alteration o...

Objective: Estrogen receptors α and β are members of the nuclear receptor family which regulate target gene expression in response to estrogens and to growth factor receptors-mediated pathways. CXCR4 is a chemokine receptor whose physiological ligand is the stromal-derived-factor-1 (SDF-1), a chemokine with proliferative and chemotactic functions. Recently, we reported that ERβ activity can be modulated by the tyrosine kinase ErbB2/ErbB3 receptors and also by th...

Background: Loss of function mutations of the type-2 vasopressin receptor (V2R) in kidney lead to nephrogenic diabetes insipidus (NDI). The function of mutant receptors can be rescued using ligands resulting sufficient amount of plasma membrane localized V2Rs in a conformation which are able to generate cAMP signal. We examined a previously described, not characterized mutation. In order to determine personalized therapy for the individual the properties of the mutant receptor...

Background: Intermittent fasting increase maximum lifespan in several species and this effect is associated with reduced protein synthesis signaling. During fasting, a progressive loss of protein in human skeletal muscle is evident. Furthermore, fasting is associated with increased lipid oxidation and insulin resistance.Aim: To define which protein metabolic mechanisms are activated in skeletal muscle during fasting.Methods: We inv...

Patients suffering from low-grade chronic inflammatory diseases such as rheumatoid arthritis, osteoarthritis, diabetes and obesity have low plasma SHBG levels. These diseases are characterized among other features by high plasma IL1β levels. The aim of the present study is to explore whether IL1β could regulate hepatic SHBG production to account for low SHBG levels in these diseases. We provide evidence that daily IL1β treatment reduces SHBG production in HepG2 ...

Introduction: Hypothalamic AMP-activated protein kinase (AMPK) has emerged as a key molecular player in energy homeostasis. It participates of glucose homeostasis modulating liver glucose production. It is known that endotoxin shock presents various complicated metabolic aspects. Among them, in later phase circulatory collapse and hypoglycemia are induced with a deterioration of energy metabolism. Here we evaluated the participation of hypothalamic AMPK in the modulation of he...

It is generally accepted that hepatic responses to α-adrenergic agonists are dependent on the redistribution of intracellular and also extracellular Ca2+. Besides, phenylephrine induces significant K+ flux changes and plasma membrane hyperpolarisation. Earlier it was shown that K+ channel blockers as well as chelating of extracellular Ca2+ with EGTA could inhibit phenylephrine-induced metabolic responses and activation of mitoch...

Background: Chronic kidney disease (CKD) in human has been believed to decrease muscle weight and physical performance. High protein diet would increase muscle mass and strength especially in athletes, but is not recommended for CKD patients because of the risk for exacerbation of uremia. Therefore, we investigated the muscle character especially focused on the mitochondrial activity and physical performance in 5/6 nephrectomy CKD model mice, which fed on different protein con...

Introduction: Postoperative sepsis exhibits high mortality. Prevention of postoperative infection and palliation of sepsis symptom are important issues in the patient’s care after surgical operation. Adipose tissue as an endocrine organ that secretes various cytokines. Circulating adiponectin, an anti-inflammatory cytokine, and inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α are derived partially from adipose tissues. Recent studie...

Introduction: C-reactive protein (CRP), an acute reactant protein and member of the pentraxins family has a primitive defense function against exogenous organisms. Although its production is predominantly under the control of IL-6, IL-1 and tumor necrotic factor also contribute to hepatic synthesis and CRP secretion. CRP is mainly produced in the liver and possibly other tissues, such as atherosclerotic lesions. C-reactive protein (CRP) is associated with increased risk for ca...