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Journal of Molecular Endocrinology

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https://www.readbyqxmd.com/read/29921568/lipocalin-2-regulates-retinoic-acid-induced-activation-of-beige-adipocytes
#1
Jessica A Deis, Hong Guo, Yingjie Wu, Chengyu Liu, David A Bernlohr, Xiaoli Chen
Lipocalin-2 (Lcn2) has been previously characterized as an adipokine regulating thermogenic activation of brown adipose tissue and retinoic acid (RA)-induced thermogenesis in mice. The objective of this study was to explore the role and mechanism for Lcn2 in the recruitment and retinoic acid-induced activation of brown-like or "beige" adipocytes. We found Lcn2 deficiency reduces key markers of thermogenesis including uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in inguinal white adipose tissue (iWAT) and inguinal adipocytes derived from Lcn2-/- mice...
June 19, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29899079/hormone-therapy-and-breast-cancer-emerging-steroid-receptor-mechanisms
#2
Meghan Samantha Perkins, Renate Louw-du Toit, Donita Africander
Although hormone therapy is widely used by millions of women to relieve symptoms of menopause, it has been associated with several side-effects such as coronary heart disease, stroke and increased invasive breast cancer risk. These side-effects have caused many women to seek alternatives to conventional hormone therapy, including the controversial custom-compounded bioidentical hormone therapy suggested to not increase breast cancer risk. Historically estrogens and the estrogen receptor were considered the principal factors promoting breast cancer development and progression, however, a role for other members of the steroid receptor family in breast cancer pathogenesis is now evident, with emerging studies revealing an interplay between some steroid receptors...
June 13, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29875122/recent-insight-into-the-correlation-of-srebp-mediated-lipid-metabolism-and-innate-immune-response
#3
Hyeon Young Park, Hye Suk Kang, Seung-Soon Im
Fatty acids are essential nutrients that contribute to several intracellular functions. Fatty acid synthesis and oxidation are known to be regulated by sterol regulatory element-binding proteins (SREBPs), which play a pivotal role in the regulation of cellular triglyceride synthesis and cholesterol biogenesis. Recent studies point to a multifunctional role of SREBPs in the pathogenesis of metabolic diseases, such as obesity, type II diabetes, and cancer as well as in immune responses. Notably, fatty-acid metabolic intermediates are involved in energy homeostasis and pathophysiological conditions...
June 6, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29866650/nfatc3-deficiency-reduces-the-classical-activation-of-adipose-tissue-macrophages
#4
Li Hu, Fengli He, Meifeng Huang, Meihua Peng, Zhiguang Zhou, Feng Liu, Yan-Shan Dai
Nuclear factors of activated T-cells (NFAT) c3 has a prominent role in regulation of proinflammatory factors in immune cells. The classically activated M1 macrophages are key players in the initiation and maintenance of adipose tissue (AT) inflammation. The role of NFATc3 in obesity and AT inflammation is unknown. We set out to determine how deficiency of NFATc3 effected macrophage polarization, inflammation and insulin resistance in visceral adipose tissue of high fat diet (HFD)-fed mice. Nfatc3-/- and wild type (WT) mice were fed a HFD for 8 to 17 weeks...
June 4, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29848626/the-emergence-of-the-nicotinamide-riboside-kinases-in-the-regulation-of-nad-metabolism
#5
Rachel S Fletcher, Gareth Lavery
The concept of replenishing or elevating nicotinamide adenine dinucleotide (NAD+) availability to combat metabolic disease and ageing (described extensively in recent reviews [1, 2]) is an area of intense research. This has led to a need to define the endogenous regulatory pathways and mechanisms cell and tissues utilise to maximise NAD+ availability such that strategies to intervene in the clinical setting are able to be fully realised. This review discusses the importance of different salvage pathways involved in metabolising the vitamin B3 class of NAD+ precursor molecules, with a particular focus on the recently identified nicotinamide riboside kinase (NRK) pathway at both a tissue-specific and systemic level...
May 30, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29848625/the-mitochondrial-unfolded-protein-response-and-mitohormesis-a-perspective-on-metabolic-diseases
#6
Hyon-Seung Yi, Joon Young Chang, Minho Shong
Mitochondria perform essential roles as crucial organelles for cellular and systemic energy homeostasis, and as signaling hubs which coordinate nuclear transcriptional responses to the intra- and extra-cellular environment. Complex human diseases, including diabetes, obesity, fatty liver disease and aging-related degenerative diseases are associated with alterations in mitochondrial oxidative phosphorylation (OxPhos) function. However, a recent series of studies in animal models have revealed that an integrated response to tolerable mitochondrial stress appears to render cells less susceptible to subsequent aging processes and metabolic stresses, which is a key feature of mitohormesis...
May 30, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29764919/insights-into-steroid-sulfation-and-desulfation-pathways
#7
Paul A Foster, Jonathan Wolf Mueller
Sulfation and desulfation pathways represent highly dynamic ways of shuttling, repressing and re-activating steroid hormones, thus controlling their immense biological potency at the very heart of endocrinology. This theme currently experiences growing research interest from various sides, including, but not limited to, novel insights about PAPS synthase and sulfotransferase function and regulation, novel analytics for steroid conjugate detection and quantification. Within this review, we will also define how sulfation pathways are ripe for drug development strategies, which have translational potential to treat a number of conditions, including chronic inflammatory diseases and steroid-dependent cancers...
May 15, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29743295/defining-the-tissue-specific-roles-of-igf1-igf1r-in-regulating-metabolism-using-the-cre-loxp-system
#8
Rhonda D Kineman, Mercedes Del Rio-Moreno, André Sarmento-Cabral
It is clear that IGF1 is important in supporting growth and regulating metabolism. The IGF1 found in the circulation is primarily produced by the liver hepatocytes, but healthy mature hepatocytes do not express appreciable levels of the IGF1 receptor (IGF1R). Therefore, the metabolic actions of IGF1 are thought to be mediated via extra-hepatocyte actions. Given the structural and functional homology between IGF1/IGF1R and insulin receptor (INSR) signaling, and the fact that IGF1, IGF1R and INSR are expressed in most tissues of the body, it is difficult to separate out the tissue-specific contributions of IGF1/IGF1R in maintaining whole body metabolic function...
May 9, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29743294/gene-expression-profiling-of-the-scn-in-young-and-old-rhesus-macaques
#9
Dominique Eghlidi, Selva Leticia Luna, Donald Brown, Vasilios Garyfallou, Steven Kohama, Henryk F Urbanski
In mammals, the suprachiasmatic nucleus (SCN) is the location of a master circadian pacemaker. It receives photic signals from the environment via the retinal hypothalamic tract, which play a key role in synchronizing the body's endogenously-generated circadian rhythms with the 24-hour rhythm of the environment. Therefore, it is plausible that age-related changes within the SCN contribute to the etiology of perturbed activity-rest cycles that become prevalent in humans during aging. To test this hypothesis, we used Gene Arrays and qRT-PCR to profile age-related gene expression changes within the SCN of male rhesus macaques - a pragmatic translational animal model of human aging, which similarly displays an age-related attenuation of daytime activity levels...
May 9, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29739805/igf-1-the-jekyll-hyde-of-the-aging-brain
#10
Sriram Gubbi, Gabriela Farias Quipildor, Nir Barzilai, Derek M Huffman, Sofiya Milman
The IGF-1 signaling pathway has emerged as a major regulator of the aging process, from rodents to humans. However, given the pleiotropic actions of IGF-1, its role in the aging brain remains complex and controversial. While IGF-1 is clearly essential for normal development of the central nervous system, conflicting evidence has emerged from preclinical and human studies regarding its relationship to cognitive function, as well as cerebrovascular and neurodegenerative disorders. This review delves into the current state of the evidence examining the role of IGF-1 in the aging brain, encompassing preclinical and clinical studies...
May 8, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29728424/the-non-canonical-nf-%C3%AE%C2%BAb-pathway-and-its-contribution-to-%C3%AE-cell-failure-in-diabetes
#11
Kira Meyerovich, Fernanda Ortis, Alessandra K Cardozo
The prevalence of diabetes has reached 8.8% in worldwide population and is predicted to increase up to 10,4% by 2040. Thus, there is an urgent need for the development of means to treat or prevent this major disease. Due to its role in inflammatory responses, several studies demonstrated the importance of the transcription factor NF-κB in both type 1 (T1D) and type 2 diabetes (T2D). The two major NF-κB pathways are the canonical and the non-canonical. The later pathway is activated by the NF-κB-Inducing Kinase (NIK) that triggers p100 processing into p52, which forms with RelB its main dimer...
May 4, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29720512/a-role-for-steroid-sulfatase-in-intracrine-regulation-of-endometrial-decidualisation
#12
Douglas A Gibson, Paul A Foster, Ioannis Simitsidellis, Hilary Critchley, Olympia Kelepouri, Frances Collins, Philippa T Saunders
In women, establishment of pregnancy is dependent upon 'fine-tuning' of the endometrial microenvironment which is mediated by terminal differentiation (decidualisation) of endometrial stromal fibroblasts (ESF). We have demonstrated that intracrine steroid metabolism plays a key role in regulating decidualisation and is essential for time-dependent expression of key factors required for endometrial receptivity. The primary aim of the current study was to determine whether sulfated steroids can act as precursors to bioactive sex steroids during decidualisation...
May 2, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29618488/steroid-sulfatase-inhibition-by-aryl-sulfamates-clinical-progress-mechanism-and-future-prospects
#13
Barry V L Potter
Steroid sulfatase is an emerging drug target for the endocrine therapy of hormone-dependent diseases, catalyzing estrogen sulfate hydrolysis to estrogen. Drug discovery, developing the core aryl O-sulfamate pharmacophore, has led to steroidal and non-steroidal drugs entering numerous clinical trials, with promising results in oncology and women's health. Steroidal estrogen sulfamate derivatives were the first irreversible active-site-directed inhibitors and one was developed clinically as an oral estradiol pro-drug and for endometriosis applications...
April 4, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29875198/world-leaders-describe-the-latest-in-igf-research
#14
EDITORIAL
Emily Jane Gallagher, Derek LeRoith
No abstract text is available yet for this article.
July 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29844094/papp-a-and-cancer
#15
REVIEW
Cheryl A Conover, Claus Oxvig
The zinc metalloproteinase, PAPP-A, enhances local insulin-like growth factor (IGF) action through cleavage of inhibitory IGF-binding proteins, thereby increasing IGF available for IGF receptor-mediated cell proliferation, migration and survival. In many tumors, enhanced IGF receptor signaling is associated with tumor growth, invasion and metastasis. We will first discuss PAPP-A structure and function, and post-translational inhibitors of PAPP-A expression or proteolytic activity. We will then review the evidence supporting an important role for PAPP-A in many cancers, including breast, ovarian and lung cancer, and Ewing sarcoma...
July 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29844093/c-peptide-prevents-smad3-binding-to-alpha-promoters-to-inhibit-collagen-type-iv-synthesis
#16
Yanning Li, Yan Zhong, Wenjian Gong, Xuehan Gao, Huanli Qi, Kun Liu, Jinsheng Qi
Activation of transforming growth factor β1 (TGFB1)/SMAD3 signaling may lead to additional synthesis of collagen type IV (COL4), which is a major contributor to extracellular matrix (ECM) accumulation in diabetic nephropathy (DN). C-peptide can attenuate fibrosis to have unique beneficial effects in DN. However, whether and how C-peptide affects TGFB1/SMAD3-activated COL4 synthesis is unclear. In this study, pathological changes, expression of COL4 a1-a5 chains ( Col4a1-a5 ), COL4 distribution and protein and TGFB1 and SMAD3 protein were first assessed in a rat model of diabetes...
July 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29789323/the-emerging-connections-between-igf1-the-intestinal-microbiome-lactobacillus-strains-and-bone-growth
#17
REVIEW
Pierre Poinsot, Martin Schwarzer, Noël Peretti, François Leulier
In most animal species, postnatal growth is controlled by conserved insulin/insulin-like growth factor (IGF) signaling. In mammals, juvenile growth is characterized by a longitudinal bone growth resulting from the ossification of the growth plate. This ossification is under IGF1 influence through endocrine and paracrine mechanisms. Moreover, the nutritional status has been largely described as an important factor influencing the insulin/insulin-like growth factor signaling. It is now well established that the gut microbiota modulates the nutrient availability of its host...
July 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29789322/a-missing-piece-the-spiny-mouse-and-the-puzzle-of-menstruating-species
#18
REVIEW
Nadia Bellofiore, Fiona Cousins, Peter Temple-Smith, Hayley Dickinson, Jemma Evans
We recently discovered the first known menstruating rodent. With the exception of four bats and the elephant shrew, the common spiny mouse ( Acomys cahirinus ) is the only species outside the primate order to exhibit menses. There are few widely accepted theories on why menstruation developed as the preferred reproductive strategy of these select mammals, all of which reference the evolution of spontaneous decidualisation prior to menstrual shedding. Though menstruating species share several reproductive traits, there has been no identifiable feature unique to menstruating species...
July 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29720513/glucocorticoids-antenatal-corticosteroid-therapy-and-fetal-heart-maturation
#19
REVIEW
Emma J Agnew, Jessica R Ivy, Sarah J Stock, Karen E Chapman
Glucocorticoids are essential in mammals to mature fetal organs and tissues in order to survive after birth. Hence, antenatal glucocorticoid treatment (termed antenatal corticosteroid therapy) can be life-saving in preterm babies and is commonly used in women at risk of preterm birth. While the effects of glucocorticoids on lung maturation have been well described, the effects on the fetal heart remain less clear. Experiments in mice have shown that endogenous glucocorticoid action is required to mature the fetal heart...
July 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29678908/the-lim-homeodomain-protein-isl1-mediates-the-function-of-tcf7l2-in-pancreatic-beta-cells
#20
Weijuan Shao, Vivian Szeto, Zhuolun Song, Lili Tian, Zhong-Ping Feng, M Cristina Nostro, Tianru Jin
Pancreatic β-cell Tcf7l2 deletion or its functional knockdown suggested the essential role of this Wnt pathway effector in controlling insulin secretion, glucose homeostasis and β-cell gene expression. As the LIM homeodomain protein ISL1 is a suggested Wnt pathway downstream target, we hypothesize that it mediates metabolic functions of TCF7L2. We aimed to determine the role of ISL1 in mediating the function of TCF7L2 and the incretin hormone GLP-1 in pancreatic β-cells. The effect of dominant negative TCF7L2 (TCF7L2DN) mediated Wnt pathway functional knockdown on Isl1 expression was determined in βTCFDN mouse islets and in the rat insulinoma cell line INS-1 832/13...
July 2018: Journal of Molecular Endocrinology
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