mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol
Current evidence suggests that estradiol (E2), the main ovarian steroid, modulates energy balance by regulating both feeding and energy expenditure at the central level, through the energy sensor AMP-activated protein kinase (AMPK). We hypothesized that the hypothalamic mechanistic target of rapamycin (mTOR) pathway, a well-established nutrient sensor and modulator of appetite and puberty, could also mediate the anorectic effect of E2. Our data showed that ovariectomy (OVX) elicited a marked downregulation of the mTOR signaling in the arcuate nucleus of the hypothalamus (ARC), an effect that was reversed by either E2 repla...
Source: Journal of Endocrinology - July 16, 2018 Category: Endocrinology Authors: Gonzalez-Garcia, I., Martinez de Morentin, P. B., Estevez-Salguero, A., Contreras, C., Romero-Pico, A., Ferno, J., Nogueiras, R., Dieguez, C., Tena-Sempere, M., Tovar, S., Lopez, M. Tags: Research Source Type: research

Transcriptional activity of oestrogen receptors in the course of embryo development
Oestrogens are well-known proliferation and differentiation factors that play an essential role in the correct development of sex-related organs and behaviour in mammals. With the use of the ERE-Luc reporter mouse model, we show herein that throughout mouse development, oestrogen receptors (ERs) are active starting from day 12 post conception. Most interestingly, we show that prenatal luciferase expression in each organ is proportionally different in relation to the germ layer of the origin. The luciferase content is highest in ectoderm-derived organs (such as brain and skin) and is lowest in endoderm-derived organs (such ...
Source: Journal of Endocrinology - July 16, 2018 Category: Endocrinology Authors: Della Torre, S., Rando, G., Meda, C., Ciana, P., Ottobrini, L., Maggi, A. Tags: Research Source Type: research

Mitochondrial oxidative stress in obesity: role of the mineralocorticoid receptor
Obesity is a multifaceted, chronic, low-grade inflammation disease characterized by excess accumulation of dysfunctional adipose tissue. It is often associated with the development of cardiovascular (CV) disorders, insulin resistance and diabetes. Under pathological conditions like in obesity, adipose tissue secretes bioactive molecules called ‘adipokines’, including cytokines, hormones and reactive oxygen species (ROS). There is evidence suggesting that oxidative stress, in particular, the ROS imbalance in adipose tissue, may be the mechanistic link between obesity and its associated CV and metabolic complicat...
Source: Journal of Endocrinology - July 16, 2018 Category: Endocrinology Authors: Lefranc, C., Friederich-Persson, M., Palacios-Ramirez, R., Nguyen Dinh Cat, A. Tags: Review Source Type: research

Biochemical and clinical aspects of glycogen storage diseases
The synthesis of glycogen represents a key pathway for the disposal of excess glucose while its degradation is crucial for providing energy during exercise and times of need. The importance of glycogen metabolism is also highlighted by human genetic disorders that are caused by mutations in the enzymes involved. In this review, we provide a basic summary on glycogen metabolism and some of the clinical aspects of the classical glycogen storage diseases. Disruptions in glycogen metabolism usually result in some level of dysfunction in the liver, muscle, heart, kidney and/or brain. Furthermore, the spectrum of symptoms observ...
Source: Journal of Endocrinology - July 16, 2018 Category: Endocrinology Authors: Ellingwood, S. S., Cheng, A. Tags: Review Source Type: research

Corticosteroids and the brain
The brain is continuously exposed to varying levels of adrenal corticosteroid hormones such as corticosterone in rodents and cortisol in humans. Natural fluctuations occur due to ultradian and circadian variations or are caused by exposure to stressful situations. Brain cells express two types of corticosteroid receptors, i.e. mineralocorticoid and glucocorticoid receptors, which differ in distribution and affinity. These receptors can mediate both rapid non-genomic and slow gene-mediated neuronal actions. As a consequence of these factors, natural (e.g. stress-induced) shifts in corticosteroid level are associated with a ...
Source: Journal of Endocrinology - July 16, 2018 Category: Endocrinology Authors: Joels, M. Tags: Review Source Type: research

Critical role for the Tsc1-mTORC1 pathway in {beta}-cell mass in Pdx1-deficient mice
Mutations in the pancreatic duodenal homeobox (PDX1) gene are associated with diabetes in humans. Pdx1-haploinsufficient mice also develop diabetes, but the molecular mechanism is unknown. To this end, we knocked down Pdx1 gene expression in mouse MIN6 insulinoma cells. Pdx1 suppression not only increased apoptotic cell death but also decreased cell proliferation, which was associated with a decrease in activity of mechanistic target of rapamycin complex 1 (mTORC1). We found that in Pdx1-deficient mice, tuberous sclerosis 1 (Tsc1) ablation in pancreatic β-cells restores β-cell mass, increases β-cell prolifer...
Source: Journal of Endocrinology - July 2, 2018 Category: Endocrinology Authors: Sun, J., Mao, L., Yang, H., Ren, D. Tags: Research Source Type: research

The delayed effects of antibiotics in type 2 diabetes, friend or foe?
An increasing amount of evidence suggests that the delayed effect of antibiotics (abx) on gut microbiota after its cessation is not as favorable as its immediate effect on host metabolism. However, it is not known how the diverse abx-dependent metabolic effects influence diabetic subjects and how gut microbiota is involved. Here, we treated db/db mice with abx cocktail for 12 days and discontinued for 24 days. We found that db/db mice showed decreased body weight and blood glucose after abx treatment, which rapidly caught up after abx cessation. Twenty-four days after abx withdrawal, db/db mice exhibit increased plasma, he...
Source: Journal of Endocrinology - July 2, 2018 Category: Endocrinology Authors: Fu, L., Qiu, Y., Shen, L., Cui, C., Wang, S., Wang, S., Xie, Y., Zhao, X., Gao, X., Ning, G., Nie, A., Gu, Y. Tags: Research Source Type: research

ER{alpha} expression in T lymphocytes is dispensable for estrogenic effects in bone
In conclusion, ERα expression in T lymphocytes is dispensable for normal estrogenic regulation of bone mass in female mice. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - July 2, 2018 Category: Endocrinology Authors: Gustafsson, K. L., Nilsson, K. H., Farman, H. H., Andersson, A., Lionikaite, V., Henning, P., Wu, J., Windahl, S. H., Islander, U., Moverare-Skrtic, S., Sjogren, K., Carlsten, H., Gustafsson, J.-A., Ohlsson, C., Lagerquist, M. K. Tags: Research Source Type: research

Are peptide conjugates the golden therapy against obesity?
Obesity is a worldwide pandemic, which can be fatal for the most extremely affected individuals. Lifestyle interventions such as diet and exercise are largely ineffective and current anti-obesity medications offer little in the way of significant or sustained weight loss. Bariatric surgery is effective, but largely restricted to only a small subset of extremely obese patients. While the hormonal factors mediating sustained weight loss and remission of diabetes by bariatric surgery remain elusive, a new class of polypharmacological drugs shows potential to shrink the gap in efficacy between a surgery and pharmacology. In es...
Source: Journal of Endocrinology - July 2, 2018 Category: Endocrinology Authors: Brandt, S. J., Kleinert, M., Tschop, M. H., Muller, T. D. Tags: Review Source Type: research

The role of orexin in controlling the activity of the adipo-pancreatic axis
Orexin A and B are two neuropeptides, which regulate a variety of physiological functions by interacting with central nervous system and peripheral tissues. Biological effects of orexins are mediated through two G-protein-coupled receptors (OXR1 and OXR2). In addition to their strong influence on the sleep–wake cycle, there is growing evidence that orexins regulate body weight, glucose homeostasis and insulin sensitivity. Furthermore, orexins promote energy expenditure and protect against obesity by interacting with brown adipocytes. Fat tissue and the endocrine pancreas play pivotal roles in maintaining energy homeo...
Source: Journal of Endocrinology - July 2, 2018 Category: Endocrinology Authors: Skrzypski, M., Billert, M., Nowak, K. W., Strowski, M. Z. Tags: Review Source Type: research

Chemerin: a multifaceted adipokine involved in metabolic disorders
Metabolic syndrome is a global public health problem and predisposes individuals to obesity, diabetes and cardiovascular disease. Although the underlying mechanisms remain to be elucidated, accumulating evidence has uncovered a critical role of adipokines. Chemerin, encoded by the gene Rarres2, is a newly discovered adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism. In humans, local and circulating levels of chemerin are positively correlated with BMI and obesity-related biomarkers. In this review, we discuss both peripheral and central roles of chemerin in regulating body metabolism. In ...
Source: Journal of Endocrinology - July 2, 2018 Category: Endocrinology Authors: Helfer, G., Wu, Q.-F. Tags: Review Source Type: research

INT-767 prevents NASH and promotes visceral fat brown adipogenesis and mitochondrial function
In conclusion, INT-767 significantly counteracts HFD-induced liver and fat alterations, restoring insulin sensitivity and prompting preadipocytes differentiation toward a metabolically healthy phenotype. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - June 26, 2018 Category: Endocrinology Authors: Comeglio, P., Cellai, I., Mello, T., Filippi, S., Maneschi, E., Corcetto, F., Corno, C., Sarchielli, E., Morelli, A., Rapizzi, E., Bani, D., Guasti, D., Vannelli, G. B., Galli, A., Adorini, L., Maggi, M., Vignozzi, L. Tags: Research Source Type: research

Multiple effects of cold exposure on livers of male mice
Cold exposure of mice is a common method to stimulate brown adipose tissue (BAT) activity and induce browning of white adipose tissue (WAT) that has beneficial effects on whole-body lipid metabolism, including reduced plasma triglyceride (TG) concentrations. The liver is a key regulatory organ in lipid metabolism as it can take up as well as oxidize fatty acids. The liver can also synthesize, store and secrete TGs in VLDL particles. The effects of cold exposure on murine hepatic lipid metabolism have not been addressed. Here, we report the effects of 24-h exposure to 4°C on parameters of hepatic lipid metabolism of mal...
Source: Journal of Endocrinology - June 26, 2018 Category: Endocrinology Authors: Grefhorst, A., van den Beukel, J. C., Dijk, W., Steenbergen, J., Voortman, G. J., Leeuwenburgh, S., Visser, T. J., Kersten, S., Friesema, E. C. H., Themmen, A. P. N., Visser, J. A. Tags: Research Source Type: research

The role of obesity and adipose tissue dysfunction in gestational diabetes mellitus
Gestational diabetes mellitus is defined as diabetes diagnosed in the second or third trimester of pregnancy in patients with no history of diabetes prior to gestation. It is the most common complication of pregnancy. The underlying pathophysiology shares some common features with type 2 diabetes mellitus (T2DM) combining relatively insufficient insulin secretion with increased peripheral insulin resistance. While a certain degree of insulin resistance is the physiological characteristics of the second half of pregnancy, it is significantly more pronounced in patients with gestational diabetes. Adipose tissue dysfunction a...
Source: Journal of Endocrinology - June 26, 2018 Category: Endocrinology Authors: Šimjak, P., Cinkajzlova, A., Anderlova, K., Pařizek, A., Mraz, M., Kršek, M., Haluzik, M. Tags: Review Source Type: research

Resistin inhibits neuronal autophagy through Toll-like receptor 4
Autophagy is a non-selective degradation pathway induced in energy-deprived cells and in non-starved cells by participating in cellular inflammatory responses mainly through the elimination of injured and aged mitochondria that constitute an important source of reactive oxygen species. We have previously reported that resistin/TLR4 signaling pathway induces inflammation and insulin resistance in neuronal cell. However, the impact of resistin-induced inflammation on neuronal autophagy is unknown. In the present study, we hypothesized that resistin-induced neuroinflammation could be attributed, at least partially, to the imp...
Source: Journal of Endocrinology - June 14, 2018 Category: Endocrinology Authors: Miao, J., Benomar, Y., Al Rifai, S., Poizat, G., Riffault, L., Crepin, D., Taouis, M. Tags: Research Source Type: research

Involvement of adipose tissue inflammation and dysfunction in virus-induced type 1 diabetes
The etiopathogenesis of type 1 diabetes (T1D) remains poorly understood. We used the LEW1.WR1 rat model of Kilham rat virus (KRV)-induced T1D to better understand the role of the innate immune system in the mechanism of virus-induced disease. We observed that infection with KRV results in cell influx into visceral adipose tissue soon following infection prior to insulitis and hyperglycemia. In sharp contrast, subcutaneous adipose tissue is free of cellular infiltration, whereas β cell inflammation and diabetes are observed beginning on day 14 post infection. Immunofluorescence studies further demonstrate that KRV trig...
Source: Journal of Endocrinology - June 13, 2018 Category: Endocrinology Authors: Needell, J. C., Brown, M. N., Zipris, D. Tags: Research Source Type: research

Brown adipose tissue development and function and its impact on reproduction
Although brown adipose tissue (BAT) is one of the smallest organs in the body, it has the potential to have a substantial impact on both heat production as well as fat and carbohydrate metabolism. This is most apparent at birth, which is characterised with the rapid appearance and activation of the BAT specific mitochondrial uncoupling protein (UCP)1 in many large mammals. The amount of brown fat then gradually declines with age, an adaptation that can be modulated by the thermal environment. Given the increased incidence of maternal obesity and its potential transmission to the mother’s offspring, increasing BAT act...
Source: Journal of Endocrinology - June 13, 2018 Category: Endocrinology Authors: Symonds, M. E., Aldiss, P., Dellschaft, N., Law, J., Fainberg, H. P., Pope, M., Sacks, H., Budge, H. Tags: Review Source Type: research

Androgen and estrogen actions on male physical activity: a story beyond muscle
Physical inactivity is a pandemic that contributes to several chronic diseases and poses a significant burden on health care systems worldwide. The search for effective strategies to combat sedentary behavior has led to an intensification of the research efforts to unravel the biological substrate controlling activity. A wide body of preclinical evidence makes a strong case for sex steroids regulating physical activity in both genders, albeit the mechanisms implicated remain unclear. The beneficial effects of androgens on muscle as well as on other peripheral functions might play a role in favoring adaptation to exercise. ...
Source: Journal of Endocrinology - June 13, 2018 Category: Endocrinology Authors: Jardi, F., Laurent, M. R., Dubois, V., Kim, N., Khalil, R., Decallonne, B., Vanderschueren, D., Claessens, F. Tags: Review Source Type: research

Isosteviol ameliorates diabetic cardiomyopathy in rats by inhibiting ERK and NF-{kappa}B signaling pathways
Diabetes-induced injury of myocardium, defined as diabetic cardiomyopathy (DCM), accounts for significant mortality and morbidity in diabetic population. Alleviation of DCM by a potent drug remains considerable interests in experimental and clinical researches because hypoglycemic drugs cannot effectively control this condition. Here, we explored the beneficial effects of isosteviol sodium (STVNa) on type 1 diabetes-induced DCM and the potential mechanisms involved. Male Wistar rats were induced to diabetes by injection of streptozotocin (STZ). One week later, diabetic rats were randomly grouped to receive STVNa (STZ/STVNa...
Source: Journal of Endocrinology - June 6, 2018 Category: Endocrinology Authors: Tang, S.-G., Liu, X.-Y., Ye, J.-M., Hu, T.-T., Yang, Y.-Y., Han, T., Tan, W. Tags: Research Source Type: research

Sympathetic innervation regulates macrophage activity in rats with polycystic ovary
We present functional evidence that modulation of the immune-endocrine function by peripheral sympathetic nervous system might have implications for understanding the pathophysiology of PCOS. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - May 31, 2018 Category: Endocrinology Authors: Figueroa, F., Mendoza, G., Cardozo, D., Mohamed, F., Oliveros, L., Forneris, M. Tags: Research Source Type: research

5{alpha}-dihydroprogesterone concentrations and synthesis in non-pregnant mares
In vivo and in vitro evidence indicates that the bioactive, 5α-reduced progesterone metabolite, 5α-dihydroprogesterone (DHP) is synthesized in the placenta, supporting equine pregnancy, but its appearance in early pregnancy argues for other sites of synthesis also. It remains unknown if DHP circulates at relevant concentrations in cyclic mares and, if so, does synthesis involve the non-pregnant uterus? Jugular blood was drawn daily from cyclic mares (n = 5). Additionally, ovariectomized mares (OVX) and geldings were administered progesterone (300 mg) intramuscularly. Blood was drawn before and after treatment. ...
Source: Journal of Endocrinology - May 31, 2018 Category: Endocrinology Authors: Conley, A. J., Scholtz, E. L., Legacki, E. L., Corbin, C. J., Knych, H. K., Dujovne, G. D., Ball, B. A., Moeller, B. C., Stanley, S. D. Tags: Research Source Type: research

Empowering thyroid hormone research in human subjects using OMICs technologies
OMICs subsume different physiological layers including the genome, transcriptome, proteome and metabolome. Recent advances in analytical techniques allow for the exhaustive determination of biomolecules in all OMICs levels from less invasive human specimens such as blood and urine. Investigating OMICs in deeply characterized population-based or experimental studies has led to seminal improvement of our understanding of genetic determinants of thyroid function, identified putative thyroid hormone target genes and thyroid hormone-induced shifts in the plasma protein and metabolite content. Consequently, plasma biomolecules h...
Source: Journal of Endocrinology - May 31, 2018 Category: Endocrinology Authors: Pietzner, M., Kacprowski, T., Friedrich, N. Tags: Review Source Type: research

Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice
WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiom...
Source: Journal of Endocrinology - May 31, 2018 Category: Endocrinology Authors: Funck-Brentano, T., Nilsson, K. H., Brommage, R., Henning, P., Lerner, U. H., Koskela, A., Tuukkanen, J., Cohen-Solal, M., Moverare-Skrtic, S., Ohlsson, C. Tags: Research Source Type: research

It's reticulated: the liver at the heart of atherosclerosis
Platelets play a critical role in both the initiation and progression of atherosclerosis, and even more so in the ensuing atherothrombotic complications. Low-dose aspirin remains the mainstay of antiplatelet therapy in high-risk patients by reducing the risk of myocardial ischemia, stroke or death due to cardiovascular disease. However, antiplatelet therapies lose their efficacy in people with diabetes mellitus, increasing the risk of future atherothrombotic events. The molecular mechanisms that promote platelet hyperactivity remain unclear but could be due to glycation-induced conformational changes of platelet membranes ...
Source: Journal of Endocrinology - May 29, 2018 Category: Endocrinology Authors: Nagareddy, P. R., Noothi, S. K., Flynn, M. C., Murphy, A. J. Tags: Review Source Type: research

Impacts of pre- and postnatal nutrition on glucagon regulation and hepatic signalling in sheep
In conclusion, prenatal undernutrition and postnatal overnutrition had similar long-term implications and reduced hepatic glucagon signalling. Glucagon secretory responses to propionate were, however, not related to the prenatal nutrition history, but negatively affected by the postnatal obesogenic diet. The pancreatic α-cell compared to β-cells may thus be less sensitive towards late gestation malnutrition, whereas hepatic glucagon signalling appears to be a target of prenatal programming. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - May 23, 2018 Category: Endocrinology Authors: Adhikari, B., Khanal, P., Nielsen, M. O. Tags: Research Source Type: research

Phenylmethimazole abrogates diet-induced inflammation, glucose intolerance and NAFLD
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of both metabolic and inflammatory diseases and has become the leading chronic liver disease worldwide. High-fat (HF) diets promote an increased uptake and storage of free fatty acids (FFAs) and triglycerides (TGs) in hepatocytes, which initiates steatosis and induces lipotoxicity, inflammation and insulin resistance. Activation and signaling of Toll-like receptor 4 (TLR4) by FFAs induces inflammation evident in NAFLD and insulin resistance. Currently, there are no effective treatments to specifically target inflammation associated with this disease. We ...
Source: Journal of Endocrinology - May 14, 2018 Category: Endocrinology Authors: Patton, A., Church, T., Wilson, C., Thuma, J., Goetz, D. J., Berryman, D. E., List, E. O., Schwartz, F., McCall, K. D. Tags: Research Source Type: research

Estrogen receptor subtypes dictate the proliferative nature of the mammary gland
Estrogen induces proliferation of breast epithelial cells and is responsible for breast development at puberty. This tightly regulated control is lost in estrogen-receptor-positive (ER+) breast cancers, which comprise over 70% of all breast cancers. Currently, breast cancer diagnosis and treatment considers only the α isoform of ER; however, there is a second ER, ERβ. Whilst ERα mediates estrogen-driven proliferation of the normal breast in puberty and breast cancers, ERβ has been shown to exert an anti-proliferative effect on the normal breast. It is not known how the expression of each ER (alone or ...
Source: Journal of Endocrinology - May 14, 2018 Category: Endocrinology Authors: Dall, G. V., Hawthorne, S., Seyed-Razavi, Y., Vieusseux, J., Wu, W., Gustafsson, J.-A., Byrne, D., Murphy, L., Risbridger, G. P., Britt, K. L. Tags: Research Source Type: research

APP deficiency results in resistance to obesity but impairs glucose tolerance upon high fat feeding
The amyloid precursor protein (APP) generates a number of peptides when processed through different cleavage mechanisms, including the amyloid beta peptide that is implicated in the development of Alzheimer’s disease. It is well established that APP via its cleaved peptides regulates aspects of neuronal metabolism. Emerging evidence suggests that amyloidogenic processing of APP can lead to altered systemic metabolism, similar to that observed in metabolic disease states. In the present study, we investigated the effect of APP deficiency on obesity-induced alterations in systemic metabolism. Compared with WT littermat...
Source: Journal of Endocrinology - May 14, 2018 Category: Endocrinology Authors: Czeczor, J. K., Genders, A. J., Aston-Mourney, K., Connor, T., Hall, L. G., Hasebe, K., Ellis, M., De Jong, K. A., Henstridge, D. C., Meikle, P. J., Febbraio, M. A., Walder, K., McGee, S. L. Tags: Research Source Type: research

Chorionic somatomammotropin impacts early fetal growth and placental gene expression
Several developmental windows, including placentation, must be negotiated to establish and maintain pregnancy. Impaired placental function can lead to preeclampsia and/or intrauterine growth restriction (IUGR), resulting in increased infant mortality and morbidity. It has been hypothesized that chorionic somatomammotropin (CSH) plays a significant role in fetal development, potentially by modifying maternal and fetal metabolism. Recently, using lentiviral-mediated in vivo RNA interference in sheep, we demonstrated significant reductions in near-term (135 days of gestation; dGA) fetal and placental size, and altered fetal l...
Source: Journal of Endocrinology - May 14, 2018 Category: Endocrinology Authors: Jeckel, K. J., Boyarko, A. C., Bouma, G. J., Winger, Q. A., Anthony, R. V. Tags: Research Source Type: research

Soluble Klotho causes hypomineralization in Klotho-deficient mice
The type I transmembrane protein αKlotho (Klotho) serves as a coreceptor for the phosphaturic hormone fibroblast growth factor 23 (FGF23) in kidney, while a truncated form of Klotho (soluble Klotho, sKL) is thought to exhibit multiple activities, including acting as a hormone, but whose mode(s) of action in different organ systems remains to be fully elucidated. FGF23 is expressed primarily in osteoblasts/osteocytes and aberrantly high levels in the circulation acting via signaling through an FGF receptor (FGFR)-Klotho coreceptor complex cause renal phosphate wasting and osteomalacia. We assessed the effects of exoge...
Source: Journal of Endocrinology - May 14, 2018 Category: Endocrinology Authors: Minamizaki, T., Konishi, Y., Sakurai, K., Yoshioka, H., Aubin, J. E., Kozai, K., Yoshiko, Y. Tags: Research Source Type: research

Chronic AT1 blockade improves glucose homeostasis in obese OLETF rats
Obesity is associated with the inappropriate activation of the renin-angiotensin system (RAS), which increases arterial pressure, impairs insulin secretion and decreases peripheral tissue insulin sensitivity. RAS blockade reverses these detriments; however, it is not clear whether the disease state of the organism and treatment duration determine the beneficial effects of RAS inhibition on insulin secretion and insulin sensitivity. Therefore, the objective of this study was to compare the benefits of acute vs chronic angiotensin receptor type 1 (AT1) blockade started after the onset of obesity, hyperglycemia and hypertensi...
Source: Journal of Endocrinology - May 8, 2018 Category: Endocrinology Authors: Rodriguez, R., Minas, J. N., Vazquez-Medina, J. P., Nakano, D., Parkes, D. G., Nishiyama, A., Ortiz, R. M. Tags: Research Source Type: research

Bufalin suppresses endometriosis progression by inducing pyroptosis and apoptosis
The steroid receptor coactivator (SRC)-1 isoform/estrogen receptor (ER)-β axis has an essential role in endometriosis progression. In this context, therefore, bufalin was employed as a ‘tool compound’ to evaluate inhibitors of SRC in alternative endometriosis treatment. Bufalin effectively suppressed the growth of primary human endometrial stroma cells isolated from endometriosis patients compared to women without endometriosis and immortalized human endometrial epithelial and stromal cells expressing the SRC-1 isoform compared to their parental cells in vitro. In vivo, compared to the vehicle, bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 Category: Endocrinology Authors: Cho, Y. J., Lee, J. E., Park, M. J., OMalley, B. W., Han, S. J. Tags: Research Source Type: research

Adipose and skeletal muscle thermogenesis: studies from large animals
The balance between energy intake and energy expenditure establishes and preserves a ‘set-point’ body weight. The latter is comprised of three major components including metabolic rate, physical activity and thermogenesis. Thermogenesis is defined as the cellular dissipation of energy via heat production. This process has been extensively characterised in brown adipose tissue (BAT), wherein uncoupling protein 1 (UCP1) creates a proton leak across the inner mitochondrial membrane, diverting protons away from ATP synthesis and resulting in heat dissipation. In beige adipocytes and skeletal muscle, thermogenesis c...
Source: Journal of Endocrinology - April 27, 2018 Category: Endocrinology Authors: Fuller-Jackson, J.-P., Henry, B. A. Tags: Review Source Type: research

Actions of pituitary hormones beyond traditional targets
Studies over the past decade have challenged the long-held belief that pituitary hormones have singular functions in regulating specific target tissues, including master hormone secretion. Our discovery of the action of thyroid-stimulating hormone (TSH) on bone provided the first glimpse into the non-traditional functions of pituitary hormones. Here we discuss evolving experimental and clinical evidence that growth hormone (GH), follicle-stimulating hormone (FSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin and arginine vasopressin (AVP) regulate bone and other target tissues, such as fat. Notably, genetic and...
Source: Journal of Endocrinology - April 26, 2018 Category: Endocrinology Authors: Zaidi, M., New, M. I., Blair, H. C., Zallone, A., Baliram, R., Davies, T. F., Cardozo, C., Iqbal, J., Sun, L., Rosen, C. J., Yuen, T. Tags: Review Source Type: research

Low-protein diet in puberty impairs testosterone output and energy metabolism in male rats
We examined the long-term effects of protein restriction during puberty on the function of hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axes in male rats. Male Wistar rats from the age of 30 to 60 days were fed a low-protein diet (4%, LP). A normal-protein diet (20.5%) was reintroduced to rats from the age of 60 to 120 days. Control rats were fed a normal-protein diet throughout life (NP). Rats of 60 or 120 days old were killed. Food consumption, body weight, visceral fat deposits, lipid profile, glycemia, insulinemia, corticosteronemia, adrenocorticotropic hormone (...
Source: Journal of Endocrinology - April 24, 2018 Category: Endocrinology Authors: de Oliveira, J. C., de Moura, E. G., Miranda, R. A., de Moraes, A. M. P., Barella, L. F., da Conceicao, E. P. S., Gomes, R. M., Ribeiro, T. A., Malta, A., Martins, I. P., Franco, C. C. d. S., Lisboa, P. C., Mathias, P. C. d. F. Tags: Research Source Type: research

Leptin stimulates aromatase in the growth plate: limiting catch-up growth efficiency
Catch-up growth (CUG) in childhood is defined as periods of growth acceleration, after the resolution of growth attenuation causes, bringing the children back to their original growth trajectory. Sometimes, however, CUG is incomplete, leading to permanent growth deficit and short stature. The aim of this study was to investigate the mechanisms that limit nutritional-CUG. Specifically, we focused on the crosstalk between leptin, increased by re-feeding, and sex hormones, which increase with age. In vivo studies were performed in young male Sprague Dawley rats fed ad libitum or subjected to 10/36 days of 40% food restriction...
Source: Journal of Endocrinology - April 24, 2018 Category: Endocrinology Authors: Masarwi, M., Shamir, R., Phillip, M., Gat-Yablonski, G. Tags: Research Source Type: research

Neuronostatin exerts actions on pituitary that are unique from its sibling peptide somatostatin
This study used baboon (Papio anubis) primary pituitary cell cultures, a species that closely models human physiology, to demonstrate that neuronostatin inhibits basal, but not ghrelin-/GnRH-stimulated, growth hormone (GH) and luteinizing hormone (LH) secretion in a dose- and time-dependent fashion, without affecting the secretion of other pituitary hormones (prolactin, ACTH, FSH, thyroid-stimulating hormone (TSH)) or changing mRNA levels. Actions of neuronostatin differs from somatostatin which in this study reduced GH/PRL/ACTH/LH/TSH secretion and GH/PRL/POMC/LH gene expression. Remarkably, we found that inhibitory actio...
Source: Journal of Endocrinology - April 24, 2018 Category: Endocrinology Authors: Luque, R. M., Kineman, R. D. Tags: Research Source Type: research

Sex steroid hormones as neuroprotective elements in ischemia models
We describe updated data from receptor and signaling events triggered by both hormones, with an emphasis on the mechanisms that have been reported as ‘rapid’ or ‘cytoplasmic actions’. Data showing the therapeutic effects of the hormones, used alone or in combination, are also summarized, with a focus on rodent models of middle cerebral artery occlusion (MCAO). Finally, we draw attention to evidence that neuroprotection by both hormones might be due to a combination of ‘cytoplasmic’ and ‘nuclear’ signaling. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - April 13, 2018 Category: Endocrinology Authors: Cespedes Rubio, A. E., Perez-Alvarez, M. J., Lapuente Chala, C., Wandosell, F. Tags: Review Source Type: research

Muscarinic M2 receptor promotes vasopressin synthesis in mice supraoptic nuclei
Muscarinic acetylcholine receptors have been suggested to be implicated in arginine–vasopressin secretion because intracerebroventricular muscarinic agonist administration induces arginine–vasopressin release into the circulation. Although which subtype is involved in the regulation of arginine–vasopressin secretion is unclear, M2 receptors have been reported to be highly expressed in the hypothalamus. In the present study, M2 receptor-knockout mice were used to elucidate whether M2 receptor regulates arginine–vasopressin synthesis in the paraventricular nuclei and supraoptic nuclei of the hypothala...
Source: Journal of Endocrinology - April 13, 2018 Category: Endocrinology Authors: Nagano, H., Sobue, Y., Matsuyama, H., Saito, S., Sakai, H., Alom, F., Tanahashi, Y., Ishii, T., Unno, T. Tags: Research Source Type: research

Haloperidol ameliorates androgen-induced behavioral deficits in developing male rats
The purpose of present study was to infer the potential effects of testosterone increase in some male-based childhood-onset neuropsychiatric disorders, such as Tourette syndrome. Thus, the influence of early postnatal androgen exposure upon the neurobehaviors and its possible neural basis were investigated in the study. Male pup rats received consecutive 14-day testosterone propionate (TP) subcutaneous injection from postnatal day (PND) 7. The TP treatment produced the hyperactive motor behavior and grooming behavior as well as the increased levels of dopamine, tyrosine hydroxylase and dopamine transporter in the mesodopam...
Source: Journal of Endocrinology - April 13, 2018 Category: Endocrinology Authors: Qi, C., Ji, X., Zhang, G., Kang, Y., Huang, Y., Cui, R., Li, S., Cui, H., Shi, G. Tags: Research Source Type: research

Clusterin deficiency induces lipid accumulation and tissue damage in kidney
In this study, we examined the role of clusterin in renal lipid accumulation in clusterin-knockout mice and NRK52e tubular epithelial cells. Clusterin deficiency increased the expression of SREBP1 and its target genes and decreased malonyl-CoA decarboxylase protein levels in the kidney. Expression of the endocytic receptor, megalin, and scavenger receptor class A was increased in clusterin-deficient mice. Functional analysis of lipid metabolism also revealed that lipid uptake and triglyceride synthesis were increased and fatty acid oxidation was reduced, leading to increased lipid accumulation in clusterin-deficient mice. ...
Source: Journal of Endocrinology - April 13, 2018 Category: Endocrinology Authors: Heo, J.-Y., Kim, J.-E., Dan, Y., Kim, Y.-W., Kim, J.-Y., Cho, K. H., Bae, Y. K., Im, S.-S., Liu, K.-H., Song, I.-H., Kim, J.-R., Lee, I.-K., Park, S.-Y. Tags: Research Source Type: research

Stimulation of growth hormone by kisspeptin antagonists in ewes
Kisspeptin signalling is indispensable for fertility, stimulating gonadotropin-releasing hormone (GnRH) secretion and mediating gonadal steroid feedback on GnRH neurons. Moreover, kisspeptin neurons have been implicated in other non-reproductive neuroendocrine roles. Kisspeptin appears to also regulate growth hormone secretion but much of the data appear contradictory. We sought to clarify a potential role of kisspeptin in growth hormone (GH) regulation by examining the effect of kisspeptin antagonists on GH secretion in ewes under various physiological conditions. Our data show clear and robust increases in GH secretion f...
Source: Journal of Endocrinology - April 6, 2018 Category: Endocrinology Authors: Smith, J. T., Roseweir, A., Millar, M., Clarke, I. J., Millar, R. P. Tags: Research Source Type: research

Anti-Mullerian hormone overexpression restricts preantral ovarian follicle survival
We examined the effects of AMH overexpression on the stages of ovarian folliculogenesis, and the development of embryos, with a transgenic mouse that overexpresses human AMH in central nervous system neurons under the control of the mouse Thy1.2 promoter (Thy1.2-AMH Tg mice). These mice are severely sub-fertile, despite relatively normal ovulation rates. The embryos of Thy1.2-AMHTg females exhibited delayed preimplantation development and extensive mid-gestation fetal resorption. Young Thy1.2-AMHTg mouse ovaries exhibited only a slight reduction in the rate of primordial follicle activation but large declines in the number...
Source: Journal of Endocrinology - April 3, 2018 Category: Endocrinology Authors: Pankhurst, M. W., Kelley, R. L., Sanders, R. L., Woodcock, S. R., Oorschot, D. E., Batchelor, N. J. Tags: Research Source Type: research

FGF21 acts as a negative regulator of bile acid synthesis
Fibroblast growth factor 21 (FGF21) is a potent regulator of glucose and lipid homeostasis in vivo; its most closely related subfamily member, FGF19, is known to be a critical negative regulator of bile acid synthesis. To delineate whether FGF21 also plays a functional role in bile acid metabolism, we evaluated the effects of short- and long-term exposure to native FGF21 and long-acting FGF21 analogs on hepatic signal transduction, gene expression and enterohepatic bile acid levels in primary hepatocytes and in rodent and monkey models. FGF21 acutely induced ERK phosphorylation and inhibited Cyp7A1 mRNA expression in prima...
Source: Journal of Endocrinology - April 3, 2018 Category: Endocrinology Authors: Chen, M. M., Hale, C., Stanislaus, S., Xu, J., Veniant, M. M. Tags: Research Source Type: research

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats
Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here, we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uter...
Source: Journal of Endocrinology - April 3, 2018 Category: Endocrinology Authors: Hu, M., Zhang, Y., Feng, J., Xu, X., Zhang, J., Zhao, W., Guo, X., Li, J., Vestin, E., Cui, P., Li, X., Wu, X.-k., Brannstrom, M., Shao, L. R., Billig, H. Tags: Research Source Type: research

Inducible Wnt16 inactivation: WNT16 regulates cortical bone thickness in adult mice
In conclusion, WNT16 is a crucial regulator of cortical bone thickness in young adult and old mice. We propose that new treatment strategies targeting the adult regulation of WNT16 might be useful to reduce fracture risk at cortical bone sites. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - April 3, 2018 Category: Endocrinology Authors: Ohlsson, C., Henning, P., Nilsson, K. H., Wu, J., Gustafsson, K. L., Sjogren, K., Tornqvist, A., Koskela, A., Zhang, F.-P., Lagerquist, M. K., Poutanen, M., Tuukkanen, J., Lerner, U. H., Moverare-Skrtic, S. Tags: Research Source Type: research

Hormonal and nutritional regulation of postnatal hypothalamic development
The hypothalamus is a key centre for regulation of vital physiological functions, such as appetite, stress responsiveness and reproduction. Development of the different hypothalamic nuclei and its major neuronal populations begins prenatally in both altricial and precocial species, with the fine tuning of neuronal connectivity and attainment of adult function established postnatally and maintained throughout adult life. The perinatal period is highly susceptible to environmental insults that, by disrupting critical developmental processes, can set the tone for the establishment of adult functionality. Here, we review the m...
Source: Journal of Endocrinology - April 3, 2018 Category: Endocrinology Authors: Sominsky, L., Jasoni, C. L., Twigg, H. R., Spencer, S. J. Tags: Review Source Type: research

Fructose bisphosphatase 2 overexpression increases glucose uptake in skeletal muscle
Skeletal muscle is a major tissue for glucose metabolism and can store glucose as glycogen, convert glucose to lactate via glycolysis and fully oxidise glucose to CO2. Muscle has a limited capacity for gluconeogenesis but can convert lactate and alanine to glycogen. Gluconeogenesis requires FBP2, a muscle-specific form of fructose bisphosphatase that converts fructose-1,6-bisphosphate (F-1,6-bisP) to fructose-6-phosphate (F-6-P) opposing the activity of the ATP-consuming enzyme phosphofructokinase (PFK). In mammalian muscle, the activity of PFK is normally 100 times higher than FBP2 and therefore energy wasting cycling bet...
Source: Journal of Endocrinology - March 24, 2018 Category: Endocrinology Authors: Bakshi, I., Suryana, E., Small, L., Quek, L.-E., Brandon, A. E., Turner, N., Cooney, G. J. Tags: Research Source Type: research

Lactobacillus acidophilus NS1 attenuates diet-induced obesity and fatty liver
Obesity is a major threat to public health, and it is strongly associated with insulin resistance and fatty liver disease. Here, we demonstrated that administration of Lactobacillus acidophilus NS1 (LNS1) significantly reduced obesity and hepatic lipid accumulation, with a concomitant improvement in insulin sensitivity, in high-fat diet (HFD)-fed mice. Furthermore, administration of LNS1 inhibited the effect of HFD feeding on the SREBP-1c and PPARα signaling pathways and reduced lipogenesis with an increase in fatty acid oxidation in ex vivo livers from HFD-fed mice. These LNS1 effects were confirmed in HepG2 cells a...
Source: Journal of Endocrinology - March 24, 2018 Category: Endocrinology Authors: Park, S.-S., Lee, Y.-J., Song, S., Kim, B., Kang, H., Oh, S., Kim, E. Tags: Research Source Type: research

Vitamin D is crucial for maternal care and offspring social behaviour in rats
Early life vitamin D plays a prominent role in neurodevelopment and subsequent brain function, including schizophrenic-like outcomes and increasing evidence for an association with autism spectrum disorder (ASD). Here, we investigate how early life vitamin D deficiency during rat pregnancy and lactation alters maternal care and influences neurodevelopment and affective, cognitive and social behaviours in male adult offspring. Sprague–Dawley rats were placed on either a vitamin D control (2195 IU/kg) or deficient diet (0 IU/kg) for five weeks before timed mating, and diet exposure was maintained until weaning of offsp...
Source: Journal of Endocrinology - March 20, 2018 Category: Endocrinology Authors: Yates, N. J., Tesic, D., Feindel, K. W., Smith, J. T., Clarke, M. W., Wale, C., Crew, R. C., Wharfe, M. D., Whitehouse, A. J. O., Wyrwoll, C. S. Tags: Research Source Type: research