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Molecular and Cellular Endocrinology

Giselle Adriana Abruzzese, María Florencia Heber, María José Ferrer, Silvana Rocío Ferreira, Aimé Florencia Silva, Alicia Beatriz Motta
This study aimed to evaluate the role of prenatal hyperandrogenization in liver functions and the extent of metformin as treatment. Pregnant rats were hyperandrogenized with subcutaneous testosterone (1mg/rat) between 16 and 19 of pregnancy. Prenatally hyperandrogenized (PH) female offspring displayed, at the adult life, two phenotypes; a PH irregular ovulatory phenotype (PHiov) and a PH anovulatory (PHanov) phenotype. From day 70 to the moment of sacrifice (90 days of age), 50% of the animals of each group received a daily oral dose of 50 mg/kg of metformin...
March 14, 2019: Molecular and Cellular Endocrinology
Qiang Li, Yixing Li, Zhiwang Zhang, Huifang Kang, Lifang Zhang, Yuxiang Zhang, Lei Zhou
SEIPIN deficiency leads to a severe lipodystrophic phenotype with loss of fat tissue. Interestingly, SEIPIN knockout in non-adipocytes is reported to promote intracellular triacylglycerol (TG) accumulation. However, the underlying mechanisms remain unclear at present. Here, we have shown that SEIPIN knockdown and overexpression exert opposite effects on hepatic lipometabolism. Our experimental data suggest that depletion of SEIPIN induces an increase in intracellular TG via activation of ER stress while its overexpression triggers a decrease in the intracellular TG content via increasing PGC-1α, which drives increased mitochondrial activity...
March 11, 2019: Molecular and Cellular Endocrinology
Peter Rotwein
Insulin-like growth factor 1 (IGF1) actions are essential for somatic growth and tissue repair. IGF1 gene regulation is controlled by many inputs, with growth hormone playing a major role. In most mammals, the 6-exon IGF1/Igf1 gene produces multiple transcripts via independent activity of its promoters plus alternative RNA splicing and differential polyadenylation. Here, by analyzing public genomic and RNA-sequencing repositories, I have characterized three Australian marsupial IGF1 genes. Koala, Tasmanian devil, and wallaby IGF1 are more complicated than other mammals, as they contain up to 11 exons, and encode multiple mRNAs and predicted protein precursors, including potentially novel isoforms...
March 11, 2019: Molecular and Cellular Endocrinology
Maria Ricart-Ortega, Joan Font, Amadeu Llebaria
New technologies for spatial and temporal remote control of G protein-coupled receptors (GPCRs) are necessary to unravel the complexity of GPCR signaling in cells, tissues and living organisms. An effective approach, recently developed, consists on the design of light-operated ligands whereby light-dependent GPCR activity regulation can be achieved. In this context, the use of light provides an advantage as it combines safety, easy delivery, high resolution and it does not interfere with most cellular processes...
March 9, 2019: Molecular and Cellular Endocrinology
Taeseung Lee, Subin Yun, Ji Hoon Jeong, Tae Woo Jung
Severe inflammation in the islets is observed in obese patients with type 2 diabetes. Inflammation in the islets is caused by obesity-induced serum free fatty acids. Asprosin is a fasting-induced adipokine, which contributes to hepatic glucose production. However, the effects of asprosin on inflammation and cellular dysfunction in pancreatic β-cells remain to be elucidated. Here, we demonstrated that treatment of mouse insulinoma MIN6 cells and human primary islets containing β-cells with palmitate increased asprosin expression and secretion...
March 7, 2019: Molecular and Cellular Endocrinology
Cuiyuan Jin, Rui Zhang, Zhengwei Fu, Yuanxiang Jin
The fungicide imazalil (IMZ), an AR antagonist, has been linked to endocrine disruption in animals. Here, adult female C57BL/6 mice were administered IMZ through their drinking water at levels of 0, 0.025‰ and 0.25‰ during the gestation and lactation periods (the exposed females are marked as F0 , and the offspring are marked as F1 ). Then, we evaluated the physiological, biochemical and gene expression levels in mice after maternal IMZ exposure. The genes involved in sex hormone receptors, cholesterol synthesis and T synthesis were generally inhibited, and the serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were also decreased in the F0 generation female mice...
March 7, 2019: Molecular and Cellular Endocrinology
Feng Cai, Congxin Dai, Shasha Chen, Qun Wu, Xiaohai Liu, Yuan Hong, Zhen Wang, Li Li, Wei Yan, Renzhi Wang, Jianmin Zhang
Silencing of noncoding genes within the imprinted DLK1-MEG3 locus is exclusive to human nonfunctional pituitary adenomas (NFPAs), but the exact mechanism is still unclear. This study was designed to demonstrate the impact of CXCL12 on the expression of miRNAs within this locus and phenotypic alterations of NFPAs. Human NFPA samples were collected for screening differentially expressed miRNAs by CXCL12. Target mRNAs of the miRNAs were predicted and verified in vitro. Tumor phenotypic alterations were also tested...
March 7, 2019: Molecular and Cellular Endocrinology
Jean-Philippe Pin, Julie Kniazeff, Laurent Prézeau, Jiang-Feng Liu, Philippe Rondard
For more than twenty years now, GPCR dimers and larger oligomers have been the subject of intense debates. Evidence for a role of such complexes in receptor trafficking to and from the plasma membrane have been provided. However, one main issue is of course to determine whether or not such a phenomenon can be responsible for an allosteric and reciprocal control (allosteric control) of the subunits. Such a possibility would indeed add to the possible ways a cell integrates various signals targeting GPCRs. Among the large GPCR family, the class C receptors that include mGlu and GABAB receptors, represent excellent models to examine such a possibility as they are mandatory dimers...
March 5, 2019: Molecular and Cellular Endocrinology
Shoichi Kageyama, Kojiro Nakamura, Jerzy W Kupiec-Weglinski
No abstract text is available yet for this article.
March 3, 2019: Molecular and Cellular Endocrinology
Thomas Klonisch
No abstract text is available yet for this article.
March 1, 2019: Molecular and Cellular Endocrinology
Yeimy González-Giraldo, Diego A Forero, Valentina Echeverria, Luis Miguel Garcia-Segura, George E Barreto
Palmitic acid (PA) induces several metabolic and molecular changes in astrocytes, and, it is involved in pathological conditions related to neurodegenerative diseases. Previously, we demonstrated that tibolone, a synthetic steroid with estrogenic, progestogenic and androgenic actions, protects cells from mitochondrial damage and morphological changes induced by PA. Here, we have evaluated which estrogen receptor is involved in protective actions of tibolone and analyzed whether tibolone reverses gene expression changes induced by PA...
February 26, 2019: Molecular and Cellular Endocrinology
Graeme P Williams, Philippa D Darbre
BACKGROUND: Phenolic endocrine-disrupting compounds (EDCs) have long been suspected of increasing human breast cancer risk, via aromatase up-regulation; however, the metabolic effects upon aromatase in human breast cells exposed to environmentally relevant concentrations of phenolic compounds, have not been addressed. OBJECTIVES: To examine the mechanistic responses of aromatase CYP19A1 mRNA, aromatase activity, estradiol biosynthesis and cellular proliferation, in three human breast cell lines, exposed to seven phenolic compounds, at environmentally relevant concentrations...
February 25, 2019: Molecular and Cellular Endocrinology
Maria João Meneses, Diego O Borges, Tânia R Dias, Fátima O Martins, Pedro F Oliveira, M Paula Macedo, Marco G Alves
Insulin degrading enzyme (IDE) is a zinc metalloprotease responsible for degrading and inactivating several bioactive peptides, including insulin. Individuals without this enzyme or with a loss-of-function mutation in the gene that codifies it, present hyperinsulinemia. In addition, impairment of IDE-mediated insulin clearance is associated with the development of metabolic diseases, namely prediabetes. Although insulin regulates male fertility, the role of IDE on male reproductive function remains unknown...
February 23, 2019: Molecular and Cellular Endocrinology
Yue Wu, Li Tang, Gissou Azabdaftari, Elena Pop, Gary J Smith
Adrenal androgens dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) are potential substrates for intracrine production of testosterone (T) and dihydrotestosterone (DHT), or directly to DHT, by prostate cancer (PCa) cells. Production of DHT from DHEAS and DHEA, and the role of steroid sulfatase (STS), were evaluated ex vivo using fresh human prostate tissue and in vitro using human PCa cell lines. STS was expressed in benign prostate tissue and PCa tissue. DHEAS at a physiological concentration was converted to DHT in prostate tissue and PCa cell lines, which was STS-dependent...
February 23, 2019: Molecular and Cellular Endocrinology
A Lerner, L Owens, M Coates, C Simpson, G Poole, J Velupillai, M Liyanage, G Christopoulos, S Lavery, K Hardy, S Franks
INTRODUCTION: Aberrant function of granulosa cells has been implicated in the pathophysiology of PCOS. MATERIALS & METHODS: GL cells were collected during oocyte retrieval for IVF/ICSI. RT-qPCR was used to compare gene expression between 12 control women, 12 with ovulatory PCO and 12 with anovulatory PCOS. To examine which genes are directly regulated by androgens, GL cells from an additional 12 control women were treated in-vitro with 10 nM dihydrotestosterone (DHT)...
February 22, 2019: Molecular and Cellular Endocrinology
Liv la Cour Poulsen, Anne Lis Mikkelsen Englund, Marie Louise Muff Wissing, Claus Yding Andersen, Rehannah Borup, Marie Louise Grøndahl
Ovulation has been compared to a local inflammatory reaction. We performed an in silico study on a unique, PCR validated, transcriptome microarray study, to evaluate if known inflammatory mechanisms operate during ovulation. The granulosa cells were obtained in paired samples at two different time points during ovulation (just before and 36 h after ovulation triggering) from nine women receiving fertility treatment. A total of 259 genes related to inflammation became significantly upregulated during ovulation (2-80 fold, p < 0...
February 22, 2019: Molecular and Cellular Endocrinology
Luisa Cigliano, Maria Stefania Spagnuolo, Gaetana Napolitano, Lucia Iannotta, Gianluca Fasciolo, Daniela Barone, Paola Venditti
The cholesterol metabolite 24(S)-hydroxycholesterol (24S-OHC) allows cholesterol excretion from the brain and was suggested to be critically involved in physiological as well as neurodegenerative processes. It induces on human neuronal cell cultures a dose dependent toxicity associated with increased reactive oxygen species production. Since glial cells play a key role in assisting neuronal function, here we investigated the effects of increased concentrations of 24S-OHC on a glial cell model (human glioblastoma U-87 MG cells)...
February 22, 2019: Molecular and Cellular Endocrinology
Saúl Lira-Albarrán, Claudia C Vega, Marta Durand, Claudia Rangel, Fernando Larrea
The aim of this study was to analyze the effects of progesterone withdrawal on gene transcription in receptive endometrium by the administration of a single dose of 50 mg of the anti-progesterone receptor mifepristone (MFP) at the time of follicle rupture (FR). Six volunteer ovulatory women were studied, taking endometrial biopsies of three control and three MFP-treated women on days LH+2 (C-LH+2) and LH+7 (T-MFP), respectively. The biopsies were prepared for RNA isolation or histological and immunohistochemistry studies...
February 20, 2019: Molecular and Cellular Endocrinology
Fanjing Kong, Chenxiang Du, Yu Wang
MicroRNAs (miRNAs or miRs)-9 expression was reported to be upregulated in the follicular fluid of patients with polycystic ovary syndrome (PCOS). However, whether miR-9 affects ovarian dysfunction of PCOS and the related mechanisms are still unclear. Here we detected miR-9 and vitamin D receptor (VDR) expression in women with PCOS and controls, and investigated whether miR-9 affects ovarian granulosa cells (GCs) proliferation and apoptosis by targeting VDR. We found increased miR-9 and decreased VDR in the blood and isolated ovarian GCs of women with PCOS compared with the controls...
February 19, 2019: Molecular and Cellular Endocrinology
Amanda C Ampey, Derek S Boeldt, Luca Clemente, Mary A Grummer, FuXian Yi, Ronald R Magness, Ian M Bird
Enhancement of vasodilation of uterine arteries during pregnancy occurs through increased connexin (Cx)43 gap junction (GJ) communication supporting more frequent and sustained Ca2+ 'bursts'. Such adaptation is lacking in subjects with preeclampsia (PE). Here we show TNF-alpha, commonly increased in PE subjects, inhibits Cx43 function and Ca2+ bursts in pregnancy-derived ovine uterine artery endothelial cells (P-UAEC) via Src and MEK/ERK phosphorylation of Cx43, and this can be reversed by PP2 or U0126. Of relevance to humans: (1) the nutraceutical Src antagonist t10, c12 CLA also recovers Ca2+ bursting in P-UAEC...
February 16, 2019: Molecular and Cellular Endocrinology
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