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William C Engeland, Logan Massman, Shubhendu Mishra, J Marina Yoder, Sining Leng, Emanuele Pignatti, Mary E Piper, Diana L Carlone, David T Breault, Paulo Kofuji
The glucocorticoid (GC) rhythm is entrained to light-dark (LD) cycles via a molecular clock in the suprachiasmatic nucleus (SCN) and is maintained by an adrenal clock synchronized by SCN-dependent signals. Targeted deletion of the core clock gene Bmal1 can disrupt adrenal clock function. The requirement of the adrenal clock to stabilize the circadian GC rhythm during exposure to aberrant LD cycles was determined using novel aldosterone synthase (AS)Cre/+:: Bmal1Fl/Fl mice in which Bmal1 deletion occurred during postnatal adrenal transdifferentiation...
October 12, 2018: Endocrinology
Lisa L Koorneef, José K van den Heuvel, Jan Kroon, Mariëtte R Boon, Peter A C 't Hoen, Kristina M Hettne, Nienke M van de Velde, Kelsey B Kolenbrander, Trea C M Streefland, Isabel M Mol, Hetty C M Sips, Szymon M Kielbasa, Hailiang Mei, Joseph K Belanoff, Alberto M Pereira, Maaike H Oosterveer, Hazel Hunt, Patrick C N Rensen, Onno C Meijer
Non-alcoholic fatty liver disease (NAFLD) medication is an unmet need. Glucocorticoid stress hormones (GC) drive fat metabolism in the liver, but both full blockade and full stimulation of GC signaling aggravate NAFLD pathology. We investigated the efficacy of selective glucocorticoid receptor (GR) modulator CORT118335, that recapitulates only a subset of GC actions, in reducing liver lipid accumulation in mice. Male C57BL/6J mice received low-fat diet, or high-fat diet mixed with vehicle or CORT118335. Livers were analyzed histologically and for genome-wide mRNA expression...
October 12, 2018: Endocrinology
Alissa K Rutman, Sarita Negi, Marco Gasparrini, Craig P Hasilo, Jean Tchervenkov, Steven Paraskevas
The autoimmune response which characterizes Type 1 diabetes (T1D) has no clear cause. Extracellular vesicles (EV) play an important role in triggering the immune response in other contexts. Here, we propose a model by which EV isolated from human islets stimulate proinflammatory immune responses and lead to peripheral blood mononuclear cell (PBMC) activation. We show that human islet EV are internalized by monocytes and B cells and lead to an increase in T-helper 1, 2 and 17 cytokine expression, as well as T and B cell proliferation...
October 10, 2018: Endocrinology
Thu H Truong, Carol A Lange
Steroid hormone receptors (SR) have a multitude of functions in human biology and disease progression. The SR family of related ligand-activated transcription factors includes androgen (AR), estrogen (ER), glucocorticoid (GR), mineralocorticoid (MR), and progesterone receptors (PRs). Antiestrogen or ER-targeted therapies to block ER action remain the primary treatment for luminal breast cancers. Although this strategy is successful, approximately 40% of patients eventually relapse due to endocrine resistance...
October 10, 2018: Endocrinology
David M Irwin
No abstract text is available yet for this article.
October 9, 2018: Endocrinology
Su Young Han, Jenny Clarkson, Richard Piet, Allan E Herbison
Developments in optical imaging and optogenetics are transforming the functional investigation of neuronal networks throughout the brain. Recent studies in the neuroendocrine field have used genetic mouse models combined with a variety of light-activated optical tools as well as GCaMP calcium imaging to interrogate the neural circuitry controlling hormone secretion. The present review highlights the benefits and caveats of these approaches for undertaking both acute brain slice and functional studies in vivo...
October 9, 2018: Endocrinology
Maggie C Evans, Greg M Anderson
Optimal fertility in humans and animals relies on the availability of sufficient metabolic fuels, information about which is communicated to the brain via levels of the hormones leptin and insulin. The circadian clock system is also critical; this input is particularly evident in the precise timing of the female-specific surge of GnRH and LH secretion that triggers ovulation on the following day. Chronodisruption or metabolic imbalance can both impair reproductive activity, and these two disruptions exacerbate each other, such that they often occur simultaneously...
October 9, 2018: Endocrinology
Masayoshi Ishida, Naoyuki Kawao, Kiyotaka Okada, Kohei Tatsumi, Kazuko Sakai, Kazuto Nishio, Hiroshi Kaji
It is well known that sex differences exist about the severity of osteoporosis and bone metabolism, suggesting that factors other than sex hormones might be responsible for sex differences of bone metabolism. We therefore examined sex differences of the osteoblast phenotypes of mouse osteoblasts, and then performed the comparative gene expression analyses using a comprehensive DNA microarray between female and male osteoblasts. Alkaline phosphatase (ALP) activity, mineralization and the expression of Osterix, ALP, and bone sialoprotein were significantly lower in mouse female osteoblasts, compared to male...
October 9, 2018: Endocrinology
Jose Cordoba-Chacon, Andre Sarmento-Cabral, Mercedes Del Rio-Moreno, Alberto Diaz-Ruiz, Papasani V Subbaiah, Rhonda D Kineman
Nonalcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), is associated with reduced growth hormone (GH) input/signaling and GH therapy is effective in the reduction/resolution of NAFLD/NASH in select patient populations. Our laboratory has focused on isolating the direct vs. indirect effects of GH in preventing NAFLD/NASH. We reported that chow-fed, adult-onset hepatocyte-specific GH receptor knockdown (aHepGHRkd) mice rapidly (within 7d) develop steatosis associated with increased hepatic de novo lipogenesis (DNL), independent of changes in systemic metabolic function...
October 5, 2018: Endocrinology
Ruth A Morgan, John A Keen, Natalie Homer, Mark Nixon, Anna McKinnon-Garvin, Jodie Moses-Williams, Sarah Davis, Patrick W F Hadoke, Brian R Walker
Equine Cushing's Disease (Pituitary pars intermedia dysfunction (PPID)) is a common condition of older horses but its pathophysiology is complex and poorly understood. In contrast to pituitary-dependent hyperadrenocorticism in other species, PPID is characterised by elevated plasma ACTH but not elevated plasma cortisol. In this study, we address this paradox and the hypothesis that PPID is a syndrome of ACTH excess in which there is dysregulation of peripheral glucocorticoid metabolism and binding. In 14 PPID horses compared with 15 healthy controls, we show that: in plasma, cortisol levels and cortisol binding to CBG were not different; in urine, glucocorticoid and androgen metabolites were increased up to four-fold; in liver, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression was reduced; in peri-renal adipose tissue 11β-HSD1 and carbonyl reductase 1 expression was increased; and tissue cortisol levels were not measurably different...
October 4, 2018: Endocrinology
V Praveen Chakravarthi, Vincentaben Khristi, Subhra Ghosh, Sireesha Yerrathota, Eddie Dai, Katherine F Roby, Michael W Wolfe, M A Karim Rumi
Hypothalamic expression of Kiss1 plays an essential role in the onset of puberty, gonadal development, and ovulation. Estrogens regulate the expression of Kiss1 in the hypothalamus through ESR1. Kiss1 is also expressed in the ovary, where its expression correlates with the onset of puberty and progression of the estrous cycle. To date, estrogen regulation of Kiss1 expression in the ovary has not been investigated. We recently observed that gonadotropin-induced Kiss1 expression was absent in Esr2-null rat ovaries even though Esr1 was present...
October 1, 2018: Endocrinology
Allan E Herbison
The pulsatile release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion are essential for fertility in all mammals. Pulses of LH occur approximately every hour in follicular-phase females and every 2-3 hours in luteal-phase females and males. Many studies over the last 50 years have sought to identify the nature and mechanism of the "GnRH pulse generator" responsible for pulsatile LH release. This review examines the characteristics of pulsatile hormone release and summarizes investigations that have led to our present understanding of the GnRH pulse generator...
September 28, 2018: Endocrinology
Molly J Dickens, Jodi L Pawluski
The transition to motherhood is characterized by some of the most pronounced endocrine changes a women will experience in her lifetime. Unfortunately matrescence is also a time in a woman's life when she is most susceptible to mental illness such as perinatal depression. A growing body of research has aimed to determine how key endocrine systems, such as the hypothalamic-pituitary-adrenal (HPA) axis, are involved in the dysregulation of perinatal mental health. However, very little research has consistently linked perinatal changes in the HPA axis with maternal mental illness...
September 25, 2018: Endocrinology
Uma Maheswari Selvaraj, Kielen Zuurbier, Cody Whoolery, Erik J Plautz, Ken L Chambliss, Xiangmei Kong, Shanrong Zhang, Sung Hoon Kim, Benita S Katzenellenbogen, John A Katzenellenbogen, Chieko Mineo, Philip W Shaul, Ann M Stowe
Estrogens provide neuroprotection in animal models of stroke, but uterotrophic effects and cancer risk limit translation. Classical estrogen receptors (ER) serve as transcription factors, whereas non-nuclear ER govern numerous cell processes and exert beneficial cardiometabolic effects without uterine or breast cancer growth in mice. Here we determined how non-nuclear ER stimulation with a pathway-preferential estrogen (PaPE-1) impacts stroke outcome in mice.Ovariectomized female mice received vehicle, estradiol (E2), or PaPE-1 before and following transient middle cerebral artery occlusion (tMCAo)...
September 25, 2018: Endocrinology
Michael T Peel, Yugong Ho, Stephen A Liebhaber
The differentiation of the hormone-producing cell lineages of the anterior pituitary represents an informative model of mammalian cell fate determination. The generation and maintenance of two of these lineages, the growth hormone (GH) producing somatotropes and prolactin (PRL) producing lactotropes, are dependent on the pituitary-specific transcription factor, POU1F1. While POU1F1 is expressed in both cell types, and plays a direct role in the activation of both the Gh and Prl genes, GH expression is restricted to somatotropes and PRL expression is restricted to lactotropes...
September 21, 2018: Endocrinology
Xiaobin Han, L Darryl Quarles
No abstract text is available yet for this article.
September 20, 2018: Endocrinology
Amanda Oakie, Rennian Wang
Insulin secretion from pancreatic β-cells is initiated through channel-mediated depolarization, cytoskeletal remodeling, and vesicle tethering at the cell membrane, all of which can be regulated through cell surface receptors. Receptor tyrosine kinases (RTKs) promote β-cell development and postnatal signaling to improve β-cell mass and function, yet their activation has also been shown to initiate exocytotic events in β-cells. This review examines the role of RTK signaling in insulin secretion, with a focus on RTKs c-Kit and insulin receptor (IR)...
September 19, 2018: Endocrinology
Ishrat Jahan, Kathryn L Corbin, Avery M Bogart, Nicholas B Whitticar, Christopher D Waters, Cara Schildmeyer, Nicholas W Vann, Hannah L West, Nathan C Law, Jeffrey S Wiseman, Craig S Nunemaker
An early sign of islet failure in type 2 diabetes (T2D) is the loss of normal patterns of pulsatile insulin release. Disruptions in pulsatility are associated with a left shift in glucose sensing that can cause excessive insulin release in low glucose (relative hyperinsulinemia, a hallmark of early T2D) and beta-cell exhaustion, leading to inadequate insulin release during hyperglycemia. Our hypothesis is that reducing excessive glucokinase activity in diabetic islets improves their function. Isolated mouse islets were exposed to glucose and varying concentrations of the glucokinase inhibitor D-mannoheptulose (MH) to examine changes in intracellular calcium ([Ca2+]i) and insulin secretion...
September 18, 2018: Endocrinology
Deborah A Goldspink, Frank Reimann, Fiona M Gribble
Gut hormones produced by gastrointestinal enteroendocrine cells modulate key physiological processes including glucose homeostasis and food intake, making them potential therapeutic candidates to treat obesity and diabetes. Understanding the function of enteroendocrine cells and the molecular mechanisms driving hormone production is a key step towards mobilising endogenous hormone reserves in the gut as a new therapeutic strategy. In this review we will discuss the variety of ex vivo and in vitro model systems driving this research and their contributions to our current understanding of nutrient sensing mechanisms in enteroendocrine cells...
September 14, 2018: Endocrinology
Karin Sanders, Wesley L de Wit, Jan A Mol, Max Kurlbaum, Sabine Kendl, Matthias Kroiss, Hans S Kooistra, Sara Galac
Abiraterone acetate (AA) is a potent inhibitor of steroidogenic enzyme 17α-hydroxylase/17,20-lyase (CYP17A1). AA is approved for the treatment of prostate cancer, but could also be an interesting treatment of Cushing's syndrome (CS). Similar to humans, canine glucocorticoid synthesis requires CYP17A1, providing a useful animal model. The objective of this study was to preclinically investigate the effect of AA on adrenocortical hormone production, cell viability, and mRNA expression of steroidogenic enzymes in canine primary adrenocortical cell cultures (n = 9) from the adrenal glands of nine healthy dogs...
September 13, 2018: Endocrinology
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