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Best Practice & Research. Clinical Endocrinology & Metabolism

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https://www.readbyqxmd.com/read/29779585/translational-studies-provide-insights-for-the-etiology-and-treatment-of-cortical-bone-osteoporosis
#1
REVIEW
Robert Brommage, Claes Ohlsson
Increasing attention is being focused on the important contributions of cortical bone to bone strength, fractures and osteoporosis therapies. Recent progress in human genome wide association studies in combination with high-throughput mouse gene knockout phenotyping efforts of multiple genes and advanced conditional gene inactivation in mouse models have successfully identified genes with crucial roles in cortical bone homeostasis. Particular attention in this review is given to genes, such as WNT16, POSTN and SFRP4, that differentially affect cortical and trabecular bone architecture...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779584/imaging-endocrinology-in-animal-models-of-endocrine-disease
#2
REVIEW
Patrice Mollard, Marie Schaeffer
Endocrine organs secrete a variety of hormones involved in the regulation of a multitude of body functions. Although pancreatic islets were discovered at the turn of the 19th century, other endocrine glands remained commonly described as diffuse endocrine systems. Over the last two decades, development of new imaging techniques and genetically-modified animals with cell-specific fluorescent tags or specific hormone deficiencies have enabled in vivo imaging of endocrine organs and revealed intricate endocrine cell network structures and plasticity...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779583/mouse-models-of-peripheral-metabolic-disease
#3
REVIEW
Gabriela da Silva Xavier, David J Hodson
Metabolic disease risk is driven by defects in the function of cells that regulate energy homeostasis, as well as altered communication between the different tissues or organs that these cells occupy. Thus, it is desirable to use model organisms to understand the contribution of different cells, tissues and organs to metabolism. Mice are widely used for metabolic research, since well-characterised mouse strains (in terms of their genotype and phenotype) allow comparative studies and human disease modelling...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779582/animal-models-of-endocrine-disruption
#4
REVIEW
Heather B Patisaul, Suzanne E Fenton, David Aylor
Endocrine disrupting chemicals (EDCs) are compounds that alter the structure and function of the endocrine system and may be contributing to disorders of the reproductive, metabolic, neuroendocrine and other complex systems. Typically, these outcomes cannot be modeled in cell-based or other simple systems necessitating the use of animal testing. Appropriate animal model selection is required to effectively recapitulate the human experience, including relevant dosing and windows of exposure, and ensure translational utility and reproducibility...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779581/evidence-from-animal-models-on-the-pathogenesis-of-pcos
#5
REVIEW
K A Walters, M J Bertoldo, D J Handelsman
Polycystic ovarian syndrome (PCOS) is the most common endocrine condition in women, and is characterized by reproductive, endocrine and metabolic features. However, there is no simple unequivocal diagnostic test for PCOS, its etiology remains unknown and there is no cure. Hence, the management of PCOS is suboptimal as it relies on the ad hoc empirical management of its symptoms only. Decisive studies are required to unravel the origins of PCOS, but due to ethical and logistical reasons these are not possible in humans...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779580/animal-models-of-endometriosis-replicating-the-aetiology-and-symptoms-of-the-human-disorder
#6
REVIEW
Ioannis Simitsidellis, Douglas A Gibson, Philippa T K Saunders
Endometriosis is a chronic incurable disorder that affects 1 in 10 women of reproductive age: associated symptoms include chronic pain and infertility. The aetiology of endometriosis remains poorly understood but patients, clinicians and researchers are all in agreement that new non-surgical therapies are urgently needed to reduce the severity of symptoms. Preclinical testing of drugs requires the development and validation of models that recapitulate the key features of the disorder. In this review we describe the best-validated animal models (primate, rodent, xenograft) and their contributions to our understanding of the factors underpinning the development of symptoms...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779579/genetically-modified-mouse-models-to-investigate-thyroid-development-function-and-growth
#7
REVIEW
C Löf, K Patyra, A Kero, J Kero
The thyroid gland produces thyroid hormones (TH), which are essential regulators for growth, development and metabolism. The thyroid is mainly controlled by the thyroid-stimulating hormone (TSH) that binds to its receptor (TSHR) on thyrocytes and mediates its action via different G protein-mediated signaling pathways. TSH primarily activates the Gs -pathway, and at higher concentrations also the Gq/11 -pathway, leading to an increase of intracellular cAMP and Ca2+ , respectively. To date, the physiological importance of other G protein-mediated signaling pathways in thyrocytes is unclear...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779578/mouse-models-for-the-analysis-of-gonadotropin-secretion-and-action
#8
REVIEW
Sara Babcock Gilbert, Allyson K Roof, T Rajendra Kumar
Gonadotropins are pituitary gonadotrope-derived glycoprotein hormones. They act by binding to G-protein coupled receptors on gonads. Gonadotropins play critical roles in reproduction by regulating both gametogenesis and steroidogenesis. Although biochemical and physiological studies provided a wealth of knowledge, gene manipulation techniques using novel mouse models gave new insights into gonadotropin synthesis, secretion and action. Both gain of function and loss of function mouse models for understanding gonadotropin action in a whole animal context have already been generated...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779577/preface
#9
EDITORIAL
Matti Poutanen, Manuel Tena-Sempere
No abstract text is available yet for this article.
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678289/pathophysiology-of-melanocortin-receptors-and-their-accessory-proteins
#10
REVIEW
T V Novoselova, L F Chan, A J L Clark
The melanocortin receptors (MCRs) and their accessory proteins (MRAPs) are involved in regulation of a diverse range of endocrine pathways. Genetic variants of these components result in phenotypic variation and disease. The MC1R is expressed in skin and variants in the MC1R gene are associated with ginger hair color. The MC2R mediates the action of ACTH in the adrenal gland to stimulate glucocorticoid production and MC2R mutations result in familial glucocorticoid deficiency (FGD). MC3R and MC4R are involved in metabolic regulation and their gene variants are associated with severe pediatric obesity, whereas the function of MC5R remains to be fully elucidated...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678288/internalization-of-g-protein-coupled-receptors-implication-in-receptor-function-physiology-and-diseases
#11
REVIEW
Davide Calebiro, Amod Godbole
G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and mediate the effects of numerous hormones and neurotransmitters. The nearly 1000 GPCRs encoded by the human genome regulate virtually all physiological functions and are implicated in the pathogenesis of prevalent human diseases such as thyroid disorders, hypertension or Parkinson's disease. As a result, 30-50% of all currently prescribed drugs are targeting these receptors. Once activated, GPCRs induce signals at the cell surface...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678287/novel-mechanisms-of-g-protein-coupled-receptors-functions-at-1-angiotensin-receptor-acts-as-a-signaling-hub-and-focal-point-of-receptor-cross-talk
#12
REVIEW
András D Tóth, Gábor Turu, László Hunyady, András Balla
AT1 angiotensin receptor (AT1 R), a prototypical G protein-coupled receptor (GPCR), is the main receptor, which mediates the effects of the renin-angiotensin system (RAS). AT1 R plays a crucial role in the regulation of blood pressure and salt-water homeostasis, and in the development of pathological conditions, such as hypertension, heart failure, cardiovascular remodeling, renal fibrosis, inflammation, and metabolic disorders. Stimulation of AT1 R leads to pleiotropic signal transduction pathways generating arrays of complex cellular responses...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678286/g-protein-coupled-receptors-gpcrs-in-the-treatment-of-diabetes-current-view-and-future-perspectives
#13
REVIEW
Guido Sebastiani, Elena Ceccarelli, Maria Grazia Castagna, Francesco Dotta
G-protein coupled receptors (GPCRs) represent the largest receptor family in the genome and are of great interest for the design of novel drugs in a wide variety of diseases including neurologic disorders, obesity and Type 2 diabetes mellitus. The latter is a chronic disease characterized by insulin resistance and impaired insulin secretion, affecting >400 million patients worldwide. Here we provide an overview on: a) The molecular basis of GPCR signalling and of its involvement in the regulation of insulin secretion and of glucose homeostasis; b) the role of GPCRs in type 2 diabetes pathophysiology and as therapeutic targets of current and future glucose-lowering drugs...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678285/pharmacogenetics-of-g-protein-coupled-receptors-variants-fsh-receptor-and-infertility-treatment
#14
REVIEW
Daniele Santi, Francesco Potì, Manuela Simoni, Livio Casarini
Infertility treatment may represent a paradigmatic example of precision medicine. Follicle-stimulating hormone (FSH) has been proposed as a valuable therapeutic option both in males and in females, even if a standardized approach is far to be established. To date, several genetic mutations as well as polymorphisms have been demonstrated to significantly affect the pathophysiology of FSH-FSH receptor (FSHR) interaction, although the underlying molecular mechanisms remain unclear. This review aims to highlight possible aspects of FSH therapy that could benefit from a pharmacogenetic approach, providing an up-to-date overview of the variability of the response to FSH treatment in both sexes...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678284/aberrant-g-protein-coupled-hormone-receptor-in-adrenal-diseases
#15
REVIEW
Matthieu St-Jean, Nada El Ghorayeb, Isabelle Bourdeau, André Lacroix
The regulation of cortisol or aldosterone production when ACTH of pituitary origin or the renin-angiotensin systems are suppressed in primary adrenal Cushing's syndrome or in primary aldosteronism is exerted by diverse genetic and molecular mechanisms. In addition to recently identified mutations in various genes implicated in the cyclic AMP or ion channel pathways, steroidogenesis is not really autonomous as it is frequently regulated by the aberrant adrenocortical expression of diverse hormone receptors, particularly G-protein coupled hormone receptors (GPCR) which can substitute for the normal function of ACTH or angiotensin-II...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678283/thyrotropin-receptor-still-much-to-be-learned-from-the-patients
#16
REVIEW
Claire Briet, Valentine Suteau-Courant, Mathilde Munier, Patrice Rodien
In the absence of crystal available for the full-length thyrotropin receptor, knowledge of its structure and functioning has benefitted from the identification and characterization of mutations in patients with various thyroid dysfunctions. The characterization of activating mutations has contributed to the elaboration of a model involving the extracellular domain of the receptor as an inverse tethered agonist which, upon binding of the ligand, relieves the transmembrane domain from an inhibiting interaction and activates it...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678282/multiple-hormone-resistance-and-alterations-of-g-protein-coupled-receptors-signaling
#17
REVIEW
Mantovani Giovanna, Elli Francesca Marta
Metabolic disorders deriving from the non-responsiveness of target organs to hormones, which manifest clinically similar to the deficiency of a given hormone itself, derive from molecular alterations affecting specific hormone receptors. Pseudohypoparathyroidism (PHP) and related disorders exemplify an unusual form of hormone resistance as the underlying molecular defect is a partial deficiency of the α subunit of the stimulatory G protein (Gsα), a key regulator of cAMP signaling pathway, or, as more recently described, of downstream effector proteins of the same pathway, such as PKA regulatory subunit 1A (R1A) and phosphodyestarase type 4D (PDE4D)...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678281/an-orphan-g-protein-coupled-receptor-causes-human-gigantism-and-or-acromegaly-molecular-biology-and-clinical-correlations
#18
REVIEW
Giampaolo Trivellin, Laura C Hernández-Ramírez, Jeremy Swan, Constantine A Stratakis
X-linked acrogigantism (X-LAG) is a recently described form of familial or sporadic pituitary gigantism characterized by very early onset GH and IGF-1 excess, accelerated growth velocity, gigantism and/or acromegaloid features. Germline or somatic microduplications of the Xq26.3 chromosomal region, invariably involving the GPR101 gene, constitute the genetic defect leading to X-LAG. GPR101 encodes a class A G protein-coupled receptor that activates the 3',5'-cyclic adenosine monophosphate signaling pathway...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29678280/the-kisspeptin-receptor-a-key-g-protein-coupled-receptor-in-the-control-of-the-reproductive-axis
#19
REVIEW
Delphine Franssen, Manuel Tena-Sempere
The kisspeptin receptor, Kiss1R, also known as Gpr54, is a G protein-coupled receptor (GPCR), deorphanized in 2001, when it was recognized as canonical receptor for the Kiss1-derived peptides, kisspeptins. In 2003, inactivating mutations of Kiss1R gene were first associated to lack of pubertal maturation and hypogonadotropic hypogonadism in humans and rodents. These seminal findings pointed out the previously unsuspected, essential role of Kiss1R and its ligands in control of reproductive maturation and function...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29549961/lipids-in-human-milk
#20
REVIEW
Hans Demmelmair, Berthold Koletzko
Fat is the main energy providing component in human milk and comprising a complex mixture of different lipid species, with quantitative dominance of triglycerides. After elucidating the fatty acid composition, more recent research has looked at influencing factors and the importance of specific lipids. Here we review quantitative aspects of maternal metabolism which contribute to the milk fatty acid composition, especially considering essential fatty acids and their long chain polyunsaturated derivatives. In this context studies with stable isotopes have indicated the importance of maternal body pools for mediating the effects of diet on milk composition...
January 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
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