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Molecular and Cellular Endocrinology

Silviu Sbiera, Sabine Kendl, Isabel Weigand, Iuliu Sbiera, Martin Fassnacht, Matthias Kroiss
90 kDa heat shock proteins (Hsp90) act as protein chaperones and play a role in modulating endoplasmic reticulum (ER) stress. Hsp90 inhibitors are under clinical investigation as cancer treatment. Mitotane therapy of adrenocortical carcinoma (ACC) has been shown to act through lipid-induced ER-stress. To explore the potential of Hsp90 inhibitors in ACC as a single agent and in combination with mitotane, we analyzed two independent gene expression data sets of adrenal tumors in silico and treated the ACC cell line model NCI-H295 with Hsp90 inhibitors BIIB021 (B) and CCT18159 (C) alone and in combination with mitotane...
October 10, 2018: Molecular and Cellular Endocrinology
Galyna V Graham, J Michael Conlon, Yasser H Abdel-Wahab, Peter R Flatt
Glucagon-like peptides-1 (GLP-1)from phylogenetically ancient fish (lamprey, dogfish, ratfish, paddlefish and bowfin) and from a teleost, the rainbow trout produced concentration-dependent stimulations of insulin release from clonal β-cells and isolated mouse islets. Lamprey and paddlefish GLP-1 were the most potent and effective. Incubation of BRIN-BD11 cells with GLP-1 receptor (GLP1R) antagonist, exendin-4 (9-39) attenuated insulinotropic activity of all peptides whereas glucagon receptor (GCGR) antagonist [des-His1 ,Pro4 ,Glu9 ] glucagon amide significantly decreased the activities of lamprey and paddlefish GLP-1 only...
October 9, 2018: Molecular and Cellular Endocrinology
Jianyao Wu, Petra Henning, Klara Sjögren, Antti Koskela, Juha Tuukkanen, Sofia Movérare-Skrtic, Claes Ohlsson
Previous studies evaluating the role of the androgen receptor (AR) for bone mass have used mouse models with global or tissue-specific lifelong inactivation of the AR. However, these mouse models have the AR inactivated already early in life and the relative roles of the AR during development, sexual maturation and in adult mice cannot be evaluated separately. The aim of the present study was to determine the specific roles of the AR in bone during sexual maturation and in adult mice. The AR was conditionally ablated at four (pre-pubertal) or ten (post-pubertal) weeks of age in male mice using tamoxifen-inducible Cre-mediated recombination...
October 8, 2018: Molecular and Cellular Endocrinology
Craig S Atwood, Samuel F Ekstein
Prior to 2002, hormone replacement therapy (HRT) was considered to be an important component of postmenopausal healthcare. This was based on a plethora of basic, epidemiological and clinical studies demonstrating the health benefits of supplementation with human sex steroids. However, adverse findings from the Women's Health Initiative (WHI) studies that examined the 2 major forms of HRT in use in the US at that time - Premarin (conjugated equine estrogens; CEE) and Prempro (CEE + medroxyprogesterone acetate; MPA), cast a shadow over the use of any form of HRT...
October 8, 2018: Molecular and Cellular Endocrinology
Delphine Rousseau-Ralliard, Anne Couturier-Tarrade, René Thieme, Roselyne Brat, Audrey Rolland, Pascal Boileau, Marie-Christine Aubrière, Nathalie Daniel, Michèle Dahirel, Emilie Derisoud, Natalie Fournier, Maria Schindler, Véronique Duranthon, Bernd Fischer, Anne Navarrete Santos, Pascale Chavatte-Palmer
Tight metabolic control of type-1 diabetes is essential during gestation, but it could be crucial during the periconception period. Feto-placental consequences of maternal type-1 diabetes around the time of conception need to be explored. Using a rabbit model, type-1 diabetes was induced by alloxan 7 days before mating. Glycemia was maintained at 15-20 mmol/L with exogenous insulin injections to prevent ketoacidosis. At 4 days post-conception (dpc), embryos were collected from diabetic (D) or normoglycemic control (C) dams, respectively, and transferred into non-diabetic recipients...
October 8, 2018: Molecular and Cellular Endocrinology
Bethan Dalton, Victoria Whitmore, Olivia Patsalos, MohammadA A Ibrahim, Ulrike Schmidt, Hubertus Himmerich
BACKGROUND: Eating disorders (EDs) have been associated with alterations in cytokine concentrations and production. This review examines whether in vitro cytokine production (i) is altered in people with EDs compared to healthy participants; and (ii) changes in response to treatment? METHODS: Using PRISMA guidelines, we systematically reviewed articles reporting group comparisons or longitudinal assessments of spontaneous and/or stimulated cytokine production in vitro in EDs...
October 5, 2018: Molecular and Cellular Endocrinology
Salman Azhar, Stefanie Bittner, Jie Hu, Wen-Jun Shen, Yuan Cortez, Xiao Hao, Han Lu, Jens O Lagerstedt, Fredric B Kraemer, Jan O Johansson
Previously, apoE-derived ABCA1 agonist peptides have been shown to possess anti-atherosclerotic and possibly antidiabetic properties. Here we assessed the in vitro and in vivo actions of a second generation of ABCA1 peptide agonists, CS6253 and T6991-2, on glucose homeostasis. The results show that these two peptides improve glucose tolerance in a prediabetic diet-induced obesity mouse model by enhancing insulin secretion. It was further demonstrated that T6991-2 also improved glucose tolerance in leptin-deficient (ob/ob) mice...
October 2, 2018: Molecular and Cellular Endocrinology
Hannu Koistinen, Mariann Koel, Maire Peters, Ago Rinken, Karolina Lundin, Timo Tuuri, Juha S Tapanainen, Henrik Alfthan, Andres Salumets, Ulf-Håkan Stenman, Darja Lavogina
While human chorionic gonadotropin (hCG) appears to have an essential role in early pregnancy, it is controversial whether the hyperglycosylated form of hCG (hCG-h), which is the major hCG isoform during the first 4-5 weeks of pregnancy, is able to activate LH/hCG receptor (LHCGR). To address this, we utilized different extensively characterized hCG and hCGβ reference reagents, cell culture- and urine-derived hCG-h preparations, and an in vitro reporter system for LHCGR activation. The WHO hCG reference reagent (99/688) was found to activate LHCGR with an EC50 -value of 3...
October 2, 2018: Molecular and Cellular Endocrinology
Yinlong Zhao, Lili Zhong, Heqing Yi
The incidence of differentiated thyroid cancer (DTC) has been increasing rapidly worldwide, and the risk factors remain unclear. With the growing number of patients with DTC, the related issues have been gradually highlighted. 131 Iodide (131 I) is an important treatment for DTC and has the potential to reduce the risk of recurrence. 131 I is also an effective treatment for distant metastases of thyroid carcinoma. However, iodide metabolism dysfunction in metastatic foci causes patients to lose the opportunity of 131 I treatment...
October 1, 2018: Molecular and Cellular Endocrinology
Viktoria Y Topper, Michael P Reilly, Lauren M Wagner, Lindsay M Thompson, Ross Gillette, David Crews, Andrea C Gore
Exposures to endocrine-disrupting chemicals (EDCs) affect the development of hormone-sensitive neural circuits, the proper organization of which are necessary for the manifestation of appropriate adult social and sexual behaviors. We examined whether prenatal exposure to polychlorinated biphenyls (PCBs), a family of ubiquitous industrial contaminants detectable in virtually all humans and wildlife, caused changes in sexually-dimorphic social interactions and communications, and profiled the underlying neuromolecular phenotype...
October 1, 2018: Molecular and Cellular Endocrinology
Sergi Soriano, Manuel Castellano-Muñoz, Alex Rafacho, Paloma Alonso-Magdalena, Laura Marroquí, Antonia Ruiz-Pino, Eva Bru-Tarí, Beatriz Merino, Esperanza Irles, Melisa Bello-Pérez, Pau Iborra, Sabrina Villar-Pazos, Jean F Vettorazzi, Eduard Montanya, Raúl M Luque, Ángel Nadal, Iván Quesada
Although there is growing evidence that cortistatin regulates several functions in different tissues, its role in the endocrine pancreas is not totally known. Here, we aim to study the effect of cortistatin on pancreatic beta-cells and glucose-stimulated insulin secretion (GSIS). Exposure of isolated mouse islets to cortistatin inhibited GSIS. This effect was prevented using a somatostatin receptor antagonist. Additionally, cortistatin hyperpolarized the membrane potential and reduced glucose-induced action potentials in isolated pancreatic beta-cells...
September 24, 2018: Molecular and Cellular Endocrinology
Maria A Ahonen, P A Nidhina Haridas, Raghavendra Mysore, Martin Wabitsch, Pamela Fischer-Posovszky, Vesa M Olkkonen
MicroRNA-107 (miR-107) plays a regulatory role in obesity and insulin resistance, but the mechanisms of its function in adipocytes have not been elucidated in detail. Here we show that overexpression of miR-107 in pre- and mature human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes attenuates differentiation and lipid accumulation. Our results suggest that miR-107 controls adipocyte differentiation via CDK6 and Notch signaling. CDK6 is a validated target of miR-107 and was downregulated upon miR-107 overexpression...
September 24, 2018: Molecular and Cellular Endocrinology
Jianyao Wu, Sofia Movérare-Skrtic, Fu-Ping Zhang, Antti Koskela, Juha Tuukkanen, Jorma J Palvimo, Petra Sipilä, Matti Poutanen, Claes Ohlsson
The crucial effects of androgens on the male skeleton are at least partly mediated via the androgen receptor (AR). In addition to hormone binding, the AR activity is regulated by post-translational modifications, including SUMOylation. SUMOylation is a reversible modification in which Small Ubiquitin-related MOdifier proteins (SUMOs) are attached to the AR and thereby regulate the activity of the AR and change its interactions with other proteins. To elucidate the importance of SUMOylation of AR for male bone metabolism, we used a mouse model devoid of the two AR SUMOylation sites (ARSUM- ; K381R and K500R are substituted)...
September 24, 2018: Molecular and Cellular Endocrinology
Vincenzo Condello, Liborio Torregrossa, Chiara Sartori, Maria Denaro, Anello Marcello Poma, Paolo Piaggi, Laura Valerio, Gabriele Materazzi, Rossella Elisei, Paolo Vitti, Fulvio Basolo
Follicular Variant of Papillary Thyroid Carcinoma (FVPTC) is usually associated with a good outcome. Nevertheless, in rare cases, it develops distant metastases (1-9%). Our goal was to investigate whether mRNA and miRNA expression profiles may help distinguish between metastatic versus non-metastatic FVPTCs. Twenty-four primary FVPTCs, 12 metastatic and 12 non-metastatic, with similar clinicopathological features were selected and analyzed by nanoString nCounter technology using two distinct panels for expression analysis of 740 mRNA and 798 miRNAs...
September 24, 2018: Molecular and Cellular Endocrinology
Zaher Merhi
Vitamin D3 (1,25-dihydroxyvitamin D3, VD3) in vitro attenuates the effect of the pro-inflammatory advanced glycation end products (AGEs) on steroidogenesis in human granulosa cells (GCs) by downregulating the receptor for AGEs (RAGE). It has been shown that VD3 alone downregulates anti-Mullerian hormone (AMH) type 2 receptor (AMHR-2) gene expression and suppresses AMH-induced SMAD 1/5/8 phosphorylation in granulosa cells. However, the effect of AGEs, in the absence or presence of VD3, on AMH action in GCs has not been studied...
September 22, 2018: Molecular and Cellular Endocrinology
Trevor M Penning
Aldo-Keto-Reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase (HSD)/prostaglandin (PG) F2α synthase) is the only 17β-HSD that is not a short-chain dehydrogenase/reductase. By acting as a 17-ketosteroid reductase, AKR1C3 produces potent androgens in peripheral tissues which activate the androgen receptor (AR) or act as substrates for aromatase. AKR1C3 is implicated in the production of androgens in castration-resistant prostate cancer (CRPC) and polycystic ovarian syndrome; and is implicated in the production of aromatase substrates in breast cancer...
September 18, 2018: Molecular and Cellular Endocrinology
Daniel Musikant, Hugo Sato, Evangelina Capobianco, Verónica White, Alicia Jawerbaum, Romina Higa
Maternal diabetes programs cardiovascular alterations in the adult offspring but the mechanisms involved remain unclarified. Here, we addresed whether maternal diabetes programs cardiac alterations related to extracellular matrix remodeling in the adult offspring, as well as the role of forkhead box transcription factor 1 (FOXO1) in the induction of these alterations. The heart from adult offspring from control and streptozotocin-induced diabetic rats was evaluated. Increased glycemia, triglyceridemia and insulinemia and markers of cardiomyopathy were found in the offspring from diabetic rats...
September 11, 2018: Molecular and Cellular Endocrinology
Jaakko T Leinonen, Yu-Chia Chen, Taru Tukiainen, Pertti Panula, Elisabeth Widén
Recent genome-wide association studies and mouse models have identified LIN28B as a gene affecting several pubertal timing-related traits and vertebrate growth. However, the exact biological mechanisms underlying the associations remain unknown. We have explored the mechanisms linking LIN28B with growth regulation by combining human gene expression data with functional models. Specifically, we show that 1) pubertal timing-associated genetic variation correlates with LIN28B expression in the pituitary and hypothalamus, 2) downregulating lin28b in zebrafish embryos associates with aberrant development of kiss2-neurons, and 3) increasing lin28b expression transiently by synthetic mRNA injections during embryogenesis results in sustained enhancement of zebrafish growth...
September 7, 2018: Molecular and Cellular Endocrinology
Ana Paula Santin Bertoni, Paula Andreghetto Bracco, Rafael Paschoal de Campos, Bruna Schwengber Lutz, Beatriz Maria Assis-Brasil, Erika Laurini de Souza Meyer, Jenifer Saffi, Elizandra Braganhol, Tania Weber Furlanetto, Márcia Rosângela Wink
The incidence of papillary thyroid carcinoma (PTC) has been increasing, which raised the interest in its molecular pathways. Although the high expression of ecto-5'-nucleotidase (NT5E) gene expression and NT5E enzymatic activity in several types of cancer is associated with tumor progression, its role in PTC remains unknown. Here, we investigated the AMP hydrolysis in human normal thyroid cells and PTC cells, in primary culture, and the association of NT5E expression with clinical aspects of PTC patients. AMPase activity was higher in thyroid cells isolated from PTC, as compared to normal thyroid (P = 0...
September 2, 2018: Molecular and Cellular Endocrinology
Wen-Qi Ma, Xue-Jiao Sun, Ying Wang, Yi Zhu, Xi-Qiong Han, Nai-Feng Liu
Mitochondrial abnormalities have long been observed in the development of vascular calcification. Metformin, a member of the biguanide class of antidiabetic drugs, has recently received attention owing to new findings regarding its protective role in cardiovascular disease. Since the precise control of mitochondrial quantity and quality is critical for the survival and function of vascular smooth muscle cells (VSMCs), maintaining mitochondrial homeostasis may be a potential protective factor for VSMCs against osteoblast-like phenotypic transition...
August 29, 2018: Molecular and Cellular Endocrinology
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