Hepatic thyroid signaling of heat-stressed late pregnant and early lactating cows
During the transition between late gestation and early lactation, dairy cows experience severe metabolic stress due to the high energy and nutrient requirements of the fetus and the mammary gland. Additional thermal stress that occurs with rising temperatures during the ongoing climate change has further adverse implications on energy intake, metabolism and welfare. The thyroid hormone (TH)-mediated cellular signaling has a pivotal role in regulation of body temperature, energy intake and metabolic adaptation to heat. To distinguish between energy intake and heat stress-related effects, Holstein cows were first kept at the...
Source: Journal of Endocrinology - July 17, 2017 Category: Endocrinology Authors: Weitzel, J. M., Viergutz, T., Albrecht, D., Bruckmaier, R., Schmicke, M., Tuchscherer, A., Koch, F., Kuhla, B. Tags: Research Source Type: research

Peripheral insulin resistance in ILK-depleted mice by reduction of GLUT4 expression
The development of insulin resistance is characterized by the impairment of glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix changes are induced when the metabolic dysregulation is sustained. The present work was devoted to analyze the possible link between the extracellular-to-intracellular mediator integrin-linked kinase (ILK) and the peripheral tissue modification that leads to glucose homeostasis impairment. Mice with general depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited increased glycemia and insulinemia concurrently with a reduction of the expression and mem...
Source: Journal of Endocrinology - July 17, 2017 Category: Endocrinology Authors: Hatem-Vaquero, M., Griera, M., Garcia-Jerez, A., Luengo, A., Alvarez, J., Rubio, J. A., Calleros, L., Rodriguez-Puyol, D., Rodriguez-Puyol, M., De Frutos, S. Tags: Research Source Type: research

Treating the dysfunctional placenta
Placental dysfunction underlies major obstetric diseases such as pre-eclampsia and fetal growth restriction (FGR). Whilst there has been a little progress in prophylaxis, there are still no treatments for placental dysfunction in normal obstetric practice. However, a combination of increasingly well-described in vitro systems for studying the human placenta, together with the availability of more appropriate animal models of pre-eclampsia and FGR, has facilitated a recent surge in work aimed at repurposing drugs and therapies, developed for other conditions, as treatments for placental dysfunction. This review: (1) highlig...
Source: Journal of Endocrinology - July 17, 2017 Category: Endocrinology Authors: Sibley, C. P. Tags: Review Source Type: research

Transendothelial movement of adiponectin is restricted by glucocorticoids
In conclusion, our study identifies glucocorticoid-mediated reductions in flux of Ad across endothelial monolayers in vivo and in vitro. This suggests that impaired Ad action in target tissues, as a consequence of reduced transendothelial flux, may contribute to the glucocorticoid-induced diabetic phenotype. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - July 13, 2017 Category: Endocrinology Authors: Dang, T. Q., Yoon, N., Chasiotis, H., Dunford, E. C., Feng, Q., He, P., Riddell, M. C., Kelly, S. P., Sweeney, G. Tags: Research Source Type: research

Dexamethasone and sex regulate placental glucocorticoid receptor isoforms in mice
Maternal dexamethasone exposure in the mouse impairs placental development and programs adult disease in a sexually dimorphic manner. Glucocorticoids bind to different glucocorticoid receptor (GR) isoforms to regulate gene transcription and cellular signaling. We hypothesized that sexually dimorphic placental responses to glucocorticoids are due to differences in GR isoforms present in the placenta. Pregnant C57Bl6 mice were exposed to saline or dexamethasone from E12.5 until E14.5 (1 µg/kg/h) before the collection of placentae. Cytoplasmic and nuclear protein fractions were extracted from placentae of male and femal...
Source: Journal of Endocrinology - July 7, 2017 Category: Endocrinology Authors: Cuffe, J. S. M., Saif, Z., Perkins, A. V., Moritz, K. M., Clifton, V. L. Tags: Research Source Type: research

Glucagon-induced extracellular cAMP regulates hepatic lipid metabolism
Hormonal signals help to maintain glucose and lipid homeostasis in the liver during the periods of fasting. Glucagon, a pancreas-derived hormone induced by fasting, promotes gluconeogenesis through induction of intracellular cAMP production. Glucagon also stimulates hepatic fatty acid oxidation but the underlying mechanism is poorly characterized. Here we report that following the acute induction of gluconeogenic genes Glucose 6 phosphatase (G6Pase) and Phosphoenolpyruvate carboxykinase (Pepck) expression through cAMP-response element-binding protein (CREB), glucagon triggers a second delayed phase of fatty acid oxidation ...
Source: Journal of Endocrinology - July 5, 2017 Category: Endocrinology Authors: Lv, S., Qiu, X., Li, J., Liang, J., Li, W., Zhang, C., Zhang, Z.-N., Luan, B. Tags: Research Source Type: research

Skeletal energy homeostasis: a paradigm of endocrine discovery
Throughout the last decade, significant developments in cellular, molecular and mouse models have revealed major endocrine functions of the skeleton. More recent studies have evolved the interplay between bone-specific hormones, the skeleton, marrow adipose tissue, muscle and the brain. This review focuses on literature from the last decade, addressing the endocrine regulation of global energy metabolism via the skeleton. In addition, we will highlight several recent studies that further our knowledge of new endocrine functions of some organs; explore remaining unanswered questions; and, finally, we will discuss future dir...
Source: Journal of Endocrinology - June 25, 2017 Category: Endocrinology Authors: Suchacki, K. J., Roberts, F., Lovdel, A., Farquharson, C., Morton, N. M., MacRae, V. E., Cawthorn, W. P. Tags: Review Source Type: research

The metabolic syndrome in mice overexpressing neuropeptide Y in noradrenergic neurons
In conclusion, changes in hepatic fatty acid, cholesterol and glucose metabolism favoring energy storage contribute to the development of NPY-induced metabolic syndrome, and the effect is likely mediated by changes in sympathetic nervous system activity. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - June 25, 2017 Category: Endocrinology Authors: Ailanen, L., Ruohonen, S. T., Vahatalo, L. H., Tuomainen, K., Eerola, K., Salomaki-Myftari, H., Roytta, M., Laiho, A., Ahotupa, M., Gylling, H., Savontaus, E. Tags: Research Source Type: research

Hypothalamic effects of neonatal diet: reversible and only partially leptin dependent
Early life diet influences metabolic programming, increasing the risk for long-lasting metabolic ill health. Neonatally overfed rats have an early increase in leptin that is maintained long term and is associated with a corresponding elevation in body weight. However, the immediate and long-term effects of neonatal overfeeding on hypothalamic anorexigenic pro-opiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY) circuitry, and if these are directly mediated by leptin, have not yet been examined. Here, we examined the effects of neonatal overfeeding on leptin-mediated development of hypot...
Source: Journal of Endocrinology - June 25, 2017 Category: Endocrinology Authors: Sominsky, L., Ziko, I., Nguyen, T.-X., Quach, J., Spencer, S. J. Tags: Research Source Type: research

Effect of mitotane on mouse ovarian follicle development and fertility
In conclusion, our study highlights the key points of ovarian folliculogenesis affected by MTT and demonstrates impairment of the ovulation process with a negative impact on conception, which is nevertheless preserved. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - June 25, 2017 Category: Endocrinology Authors: Innocenti, F., Cerquetti, L., Pezzilli, S., Bucci, B., Toscano, V., Canipari, R., Stigliano, A. Tags: Research Source Type: research

Protein kinase STK25 aggravates the severity of non-alcoholic fatty pancreas disease in mice
Characterising the molecular networks that negatively regulate pancreatic β-cell function is essential for understanding the underlying pathogenesis and developing new treatment strategies for type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic fat storage, meta-inflammation, and fibrosis in liver and skeletal muscle. Here, we assessed the role of STK25 in control of progression of non-alcoholic fatty pancreas disease in the context of chronic exposure to dietary lipids in mice. We found that overexpression of STK25 in high-fat-fed transgenic mice aggra...
Source: Journal of Endocrinology - June 25, 2017 Category: Endocrinology Authors: Nunez-Duran, E., Chanclon, B., Sutt, S., Real, J., Marschall, H.-U., Wernstedt Asterholm, I., Cansby, E., Mahlapuu, M. Tags: Research Source Type: research

MiRNA-143 mediates the proliferative signaling pathway of FSH and regulates estradiol production
MicroRNAs (MiRNAs) play important regulatory roles in many cellular processes. MiR-143 is highly enriched in the mouse ovary, but its roles and underlying mechanisms are not well understood. In the current study, we show that miR-143 is located in granulosa cells of primary, secondary and antral follicles. To explore the specific functions of miR-143, we transfected miR-143 inhibitor into primary cultured granulosa cells to study the loss of function of miR-143 and the results showed that miR-143 silencing significantly increased estradiol production and steroidogenesis-related gene expression. Moreover, our in vivo and in...
Source: Journal of Endocrinology - June 25, 2017 Category: Endocrinology Authors: Zhang, L., Zhang, X., Zhang, X., Lu, Y., Li, L., Cui, S. Tags: Research Source Type: research

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development
The cDNA of the mineralocorticoid receptor (MR) was cloned 30 years ago, in 1987. At that time, spirolactone, the first generation of synthetic steroid-based MR antagonists (MRAs), which was identified in preclinical in vivo models, had already been in clinical use for 30 years. Subsequent decades of research and development by Searle & Co., Ciba-Geigy, Roussel Uclaf and Schering AG toward identifying a second generation of much more specific steroidal MRAs were all based on the initial 17-spirolactone construct. The salient example is eplerenone, first described in 1987, coincidentally with the cloning of MR cDNA. Its...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Kolkhof, P., Barfacker, L. Tags: Thematic Review Source Type: research

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Nongenomic effects via the mineralocorticoid receptor
The mineralocorticoid receptor (MR) belongs to the steroid hormone receptor family and classically functions as a ligand-dependent transcription factor. It is involved in water-electrolyte homeostasis and blood pressure regulation but independent from these effects also furthers inflammation, fibrosis, hypertrophy and remodeling in cardiovascular tissues. Next to genomic effects, aldosterone elicits very rapid actions within minutes that do not require transcription or translation and that occur not only in classical MR epithelial target organs like kidney and colon but also in nonepithelial tissues like heart, vasculature...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Ruhs, S., Nolze, A., Hubschmann, R., Grossmann, C. Tags: Thematic Review Source Type: research

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor mutations
Aldosterone and the mineralocorticoid receptor (MR) are key elements for maintaining fluid and electrolyte homeostasis as well as regulation of blood pressure. Loss-of-function mutations of the MR are responsible for renal pseudohypoaldosteronism type 1 (PHA1), a rare disease of mineralocorticoid resistance presenting in the newborn with weight loss, failure to thrive, vomiting and dehydration, associated with hyperkalemia and metabolic acidosis, despite extremely elevated levels of plasma renin and aldosterone. In contrast, a MR gain-of-function mutation has been associated with a familial form of inherited mineralocortic...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Zennaro, M.-C., Fernandes-Rosa, F. Tags: Thematic Review Source Type: research