The liver-alpha cell axis and type 2 diabetes.
Authors: Wewer Albrechtsen NJ, Pedersen J, Galsgaard KD, Winther-Sørensen M, Suppli MP, Janah L, Gromada J, Vilstrup H, Knop FK, Holst JJ Abstract Both type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) strongly associate with increasing body mass index (BMI) and together these metabolic diseases affect millions of individuals. In patients with T2D, increased secretion of glucagon (hyperglucagonemia) contributes to the diabetic hyperglycemia as proven by the significant lowering of fasting plasma glucose levels following glucagon receptor antagonist (GRA) administration. Emerging data now in...
Source: Endocrine Reviews - March 30, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule.
Authors: Yabut JM, Crane JD, Green AE, Keating DJ, Khan WI, Steinberg GR Abstract Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fa...
Source: Endocrine Reviews - March 23, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Aging and the Male Reproductive System.
Authors: Kaufman JM, Lapauw B, Mahmoud A, T'Sjoen G, Huhtaniemi IT Abstract This narrative review presents an overview of present knowledge on fertility and reproductive hormones changes in aging men, the factors driving and modulating these changes, their clinical consequences, and benefits and risks of testosterone (T) therapy. Aging is accompanied by moderate decline of gamete quality and fertility. Population mean levels show mild total T decline, SHBG increase, steeper free T decline, and moderate LH increase with important contribution of comorbidities (e.g. obesity) to these changes. Sexual symptoms and lowe...
Source: Endocrine Reviews - March 20, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Nuclear receptors: recent drug discovery for cancer therapies.
Authors: Zhao L, Zhou S, Gustafsson JÅ Abstract Nuclear receptors (NRs) are transcription factors actively involved in many aspects of human physiology and pathology, serving as sensors of stimuli, master regulators of downstream molecular events and hubs governing complex gene regulatory networks. The importance of various members of the NR superfamily in cancer has led to substantial efforts to target them therapeutically. Notably, drugs that block the action of estrogen receptor alpha (ERα) in patients with ERα+ breast cancer or the androgen receptor (AR) in prostate cancer patients have provid...
Source: Endocrine Reviews - March 16, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Clinical management of congenital hypogonadotropic hypogonadism.
Authors: Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, Raivio T, Pitteloud N Abstract The initiation and maintenance of reproductive capacity in humans is dependent upon pulsatile secretion of the hypothalamic hormone gonadtropin-releasing hormone, GnRH. Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder that results from the failure of the normal episodic GnRH secretion, leading to delayed puberty and infertility. CHH can be associated with an absent sense of smell, also termed Kallmann syndrome, or with other anomalies. CHH is characterized by rich genetic heterogeneity, with...
Source: Endocrine Reviews - January 31, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Central Mechanisms of Glucose Sensing and Counterregulation in Defense of Hypoglycemia.
Authors: Stanley S, Moheet A, Seaquist ER Abstract Glucose homeostasis requires an organism to rapidly respond to changes in plasma glucose concentrations. Iatrogenic hypoglycemia as a result of treatment with insulin or sulfonylureas is the most common cause of hypoglycemia in humans and is generally only seen in patients with diabetes who take these medications. The first response to a fall in glucose is the detection of impending hypoglycemia by hypoglycemia detecting sensors including glucose sensing neurons in the hypothalamus and other regions. This detection is then linked to a series of neural and hormonal ...
Source: Endocrine Reviews - January 30, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Genetics and Epigenetics of Gastroenteropancreatic Neuroendocrine Neoplasms.
Authors: Mafficini A, Scarpa A Abstract Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) are heterogeneous regarding site of origin, biological behavior and malignant potential. There has been a rapid increase in data publication over the last 10 years, mainly driven by high-throughput studies on pancreatic and small intestinal NETs. This review summarizes the present knowledge on genetic and epigenetic alterations. We integrated the available information from each compartment to give a pathway-based overview. This provided a summary of the critical alterations sustaining neoplastic cells. It also highlig...
Source: Endocrine Reviews - January 20, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Thyroid Dysfunction and Diabetes Mellitus : Two Closely Associated Disorders.
Authors: Biondi B, Kahaly GJ, Robertson RP Abstract Thyroid dysfunction and diabetes mellitus are closely linked. Several studies have documented the increased prevalence of thyroid disorders in patients with diabetes mellitus and viceversa. This review critically discusses the different underlying mechanisms linking type 1 and 2 diabetes and thyroid dysfunction to demonstrate that the association of these two common disorders is unlikely a simple coincidence. We assess the current state of knowledge on the central and peripheral control of thyroid hormone on food intake and glucose and lipid metabolism in target t...
Source: Endocrine Reviews - January 18, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

3-iodothyronamine - a thyroid hormone metabolite with distinct target profiles and mode of action.
Authors: Köhrle J, Biebermann H Abstract The re-discovery of the group of thyronamines (TAM), especially the first detailed description of their most prominent congener 3-iodothyronamine (3T1AM) fourteen years ago boosted research on this thyroid hormone metabolite tremendously. TAM exert actions partly opposite to and distinct from known functions of thyroid hormones. These fascinating metabolic, anapyrexic, cytoprotective and brain effects quickly evoked the hope to use hormone-derived TAM as therapeutic option. The G-protein coupled receptor (GPCR) TAAR1, a member of the trace amine-associated receptor fami...
Source: Endocrine Reviews - January 18, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Growth hormone deficiency: health and longevity.
Authors: Aguiar-Oliveira MH, Bartke A Abstract The important role of GH in the control of mammalian longevity was first deduced from extended longevity of mice with genetic GH-deficiency (GHD) or GH-resistance. Mice with isolated GHD (IGHD) due to GHRH or GHRH-R mutations, combined deficiency of GH, PRL, and TSH, or global deletion of GH receptors live longer than their normal siblings. They also exhibit multiple features of delayed and/or slower aging, accompanied by extension of healthspan. The unexpected, remarkable longevity benefit of severe endocrine defects in these animals presumably represents evolutionari...
Source: Endocrine Reviews - December 24, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

CORRIGENDUM FOR "Children Born Small for Gestational Age: Differential Diagnosis, Molecular Genetic Evaluation, and Implications".
CORRIGENDUM FOR "Children Born Small for Gestational Age: Differential Diagnosis, Molecular Genetic Evaluation, and Implications". Endocr Rev. 2018 Dec 12;: Authors: PMID: 30541072 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - December 14, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Pancreatic Islet Transplantation in Humans: Recent Progress and Future Directions.
Authors: Rickels MR, Robertson RP Abstract Pancreatic islet transplantation has become an established approach to β-cell replacement therapy for the treatment of insulin deficient diabetes. Recent progress in techniques for islet isolation, islet culture, and peri-transplant management of the islet transplant recipient have resulted in substantial improvements in metabolic and safety outcomes for patients. For patients requiring total or sub-total pancreatectomy for benign disease of the pancreas, isolation of islets from the diseased pancreas with intrahepatic transplantation of autologous islets can prevent ...
Source: Endocrine Reviews - December 14, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Growth Hormone's Links to Cancer.
Authors: Boguszewski CL, Boguszewski MCDS Abstract Several components of the GH axis are involved in tumor progression and GH-induced intracellular signaling has been strongly associated with breast cancer susceptibility in genome-wide association studies. In the general population, high IGF-I levels and low IGFBP-3 levels within the normal range are associated with the development of common malignancies, and components of the GH-IGF signaling system exhibit correlations with clinical, histopathological and therapeutic parameters in cancer patients. Despite promising findings in preclinical studies, anti-cancer the...
Source: Endocrine Reviews - December 5, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Reproductive Endocrinology of Non-Alcoholic Fatty Liver Disease.
Authors: Grossmann M, Wierman ME, Angus P, Handelsman DJ Abstract The liver and the reproductive system interact in a multifaceted bidirectional fashion. Sex steroid signaling influences hepatic endobiotic and xenobiotic metabolism and contributes to the pathogenesis of functional and structural disorders of the liver. In turn, liver function impacts on the reproductive axis via modulating sex steroid metabolism and transport to tissues via sex hormone binding globulin (SHBG). The liver senses the body's metabolic status and adapts its energy homeostasis in a sex-dependent fashion, a dimorphism signaled by the sex ...
Source: Endocrine Reviews - December 5, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Ovulation: Parallels with Inflammatory Processes.
Authors: Duffy DM, Ko C, Jo M, Brannstrom M, Curry TE Abstract The midcycle surge of luteinizing hormone (LH) sets in motion interconnected networks of signaling cascades to bring about rupture of the follicle and release of the oocyte during ovulation. Many mediators of these LH-induced signaling cascades are associated with inflammation, leading to the postulate that ovulation is similar to an inflammatory response. First responders to the LH surge are granulosa and theca cells, which produce steroids, prostaglandins, chemokines, and cytokines, which are also mediators of inflammatory processes. These mediators, ...
Source: Endocrine Reviews - December 1, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Long-term Endocrine and Metabolic consequences of Cancer Treatment: A Systematic Review.
Authors: Gebauer J, Higham C, Langer T, Denzer C, Brabant G Abstract The number of patients surviving five or more years after initial cancer diagnosis has significantly increased over the last decades due to considerable improvements in the treatment of many cancer entities. A negative consequence of this is the emergence of long-term sequelae and endocrine disorders account for a high proportion of these. These late effects can occur decades after cancer treatment and affect up to 50% of childhood cancer survivors. Multiple predisposing factors for endocrine late effects have been identified; including radiation,...
Source: Endocrine Reviews - November 28, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Gastrointestinal Malabsorption of Thyroxine.
Authors: Virili C, Antonelli A, Santaguida MG, Benvenga S, Centanni M Abstract Levothyroxine, a largely prescribed drug with a narrow therapeutic index, is often a lifelong treatment. The therapeutic efficacy of thyroxine may be marred by behavioral, pharmacologic and pathologic issues acting as interfering factors. Despite a continuous search for an optimal thyroxine treatment, a significant number of patients fail to show a complete chemical and/or clinical response to this reference dose of thyroxine. Gastrointestinal malabsorption of oral thyroxine represents an emerging cause of refractory hypothyroidism and m...
Source: Endocrine Reviews - November 28, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Starvation in the Midst of Plenty: Reflections on the History and Biology of Insulin and Leptin.
Authors: Flier JS Abstract Insulin and leptin are critical metabolic hormones that play essential but distinct roles in regulating the physiologic switch between the fed and starved states. The discoveries of insulin and leptin, in 1922 and 1994 respectively, arose out of radically different scientific environments. Despite the dearth of scientific tools available in 1922, insulin's discovery rapidly launched a life-saving therapy for what we now know to be Type I diabetes, and continually enhanced insulin therapeutics are now effectively applied to both major forms of this increasingly prevalent disease. In contra...
Source: Endocrine Reviews - October 26, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Skeletal and extra-skeletal actions of vitamin D: Current evidence and outstanding questions.
Authors: Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A, Bilezikian J Abstract The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate is primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of...
Source: Endocrine Reviews - October 16, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

The Forgotten Lipids: Triglycerides, Remnant Cholesterol, and Atherosclerotic Cardiovascular Disease Risk.
Authors: Sandesara PB, Virani SS, Fazio S, Shapiro MD Abstract Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is a well-established mediator of atherosclerosis and a key target for intervention for the primary and secondary prevention of ASCVD. However, despite significant reduction in LDL-C, patients continue to have recurrent ASCVD events. Hypertriglyceridemia maybe an important contributor of this residual risk. Observational and genetic epidemiological data strongly support a causal role of triglycerides and the cholestero...
Source: Endocrine Reviews - October 13, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Non-classical growth hormone insensitivity (GHI): characterization of mild abnormalities of GH action.
The objective of this review is to clarify the definition, identification and investigation of this clinically relevant group of growth defects. We also review the therapeutic challenges of mild GHI. PMID: 30265312 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - September 29, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Emerging biomarkers, tools, and treatments for diabetic polyneuropathy.
Authors: Bönhof GJ, Herder C, Strom A, Papanas N, Roden M, Ziegler D Abstract Diabetic neuropathy, with its major clinical sequels notably neuropathic pain, foot ulcers, and autonomic dysfunction, is associated with substantial morbidity, increased risk of mortality, and reduced quality of life. Despite its major clinical impact, diabetic neuropathy remains underdiagnosed and undertreated. Moreover, the evidence supporting a benefit for causal treatment is weak at least in patients with type 2 diabetes, and current pharmacotherapy is largely limited to symptomatic treatment options. Thus, a better understandin...
Source: Endocrine Reviews - September 28, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Pathophysiology and Individualized Treatment for Hypothalamic Obesity Following Craniopharyngioma and Other Suprasellar Tumors: A Systematic Review.
Authors: van Iersel L, Brokke KE, Adan RAH, Bulthuis LCM, van den Akker ELT, van Santen HM Abstract The development of hypothalamic obesity (HO) following craniopharyngioma (CP) and other suprasellar tumors leads to reduced patient quality of life. No treatment algorithms are currently available for management of HO. Depending on which hypothalamic nuclei are destroyed, the pathophysiologic mechanisms and clinical symptoms that contribute to HO differ among patients. Here, we review the contribution of the hypothalamus to the pathophysiologic mechanisms and symptoms underlying CP-associated HO. In addition, we perf...
Source: Endocrine Reviews - September 26, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Insulin-like growth factor-I receptor and thyroid-associated ophthalmopathy.
Authors: Smith TJ, Janssen JAMJL Abstract Thyroid-associated ophthalmopathy (TAO) is a complex disease process presumed to emerge from autoimmunity occurring in the thyroid gland, most frequently in Graves' disease (GD). It is disfiguring and potentially blinding, culminating in orbital tissue remodeling and disruption of function of structures adjacent to the eye. There are currently no medical therapies proven capable of altering the clinical outcome of TAO in randomized, placebo-controlled multicenter trials. The orbital fibroblast represents the central target for immune reactivity. Recent identification of fib...
Source: Endocrine Reviews - September 16, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Melatonin as a hormone: new physiological and clinical insights.
MELATONIN AS A HORMONE: NEW PHYSIOLOGICAL AND CLINICAL INSIGHTS. Endocr Rev. 2018 Sep 12;: Authors: Cipolla-Neto J, do Amaral FG Abstract Melatonin is a ubiquitous molecule present in almost every live being from bacteria to humans. In vertebrates, besides being produced in peripheral tissues and acting as an autocrine and paracrine signal, melatonin is centrally synthetized by a neuroendocrine organ, the pineal gland. Independently of the considered specie, pineal hormone melatonin is always produced during the night and its production and secretory episode duration is directly dependent on the length...
Source: Endocrine Reviews - September 16, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Effects of Leptin on the Skeleton.
Authors: Reid IR, Baldock PA, Cornish J Abstract Leptin originates in adipocytes, including those in bone marrow and circulates in concentrations 20- 90-fold higher than those in the cerebrospinal fluid. It has direct anabolic effects on osteoblasts and chondrocytes, but also influences bone indirectly: via the hypothalamus and sympathetic nervous system, via changes in body weight, and via effects on the production of other hormones (e.g. pituitary). Leptin's role in bone physiology is determined by the balance of these conflicting effects. Reflecting this inconsistency, the leptin-deficient mouse has reduced leng...
Source: Endocrine Reviews - September 6, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Systemic complications of acromegaly and the impact of the current treatment landscape: an update.
Authors: Gadelha MR, Kasuki L, Lim DS, Fleseriu M Abstract Acromegaly is a chronic systemic disease with many complications and is associated with increased mortality when not adequately treated. Significant advances in acromegaly treatment, as well as in the treatment of many of its complications, mainly diabetes mellitus, heart failure and arterial hypertension, were achieved in the last decades. These developments allowed change in both prevalence and severity of some acromegaly complications and furthermore resulted in a reduction of mortality. Nowadays, mortality seems to be similar to the general population i...
Source: Endocrine Reviews - September 6, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Endocrine toxicity of cancer immunotherapy targeting immune checkpoints.
Authors: Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L Abstract Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Targeting the immune checkpoints CTLA-4 and PD-1 with inhibitory antibodies has demonstrated effective and durable anti-tumor activity in subgroups of cancer patients. The United States Food and Drug Administration has approved several immune checkpoint inhibitors (ICPis) for the treatment of a broad spectrum of malignancies. Endocrinopathies have emerged as one of the most common immune-related adverse events ...
Source: Endocrine Reviews - September 6, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Atypical Femur Fractures - Review of epidemiology, relationship to bisphosphonates, prevention and clinical management.
In conclusion, AFFs can be devastating events but even under the most pessimistic assumptions, the benefit to risk ratio is highly positive for BPs particularly over the first 3-5 years of use. As our understanding of AFF increases, it is becoming increasingly possible to maximize BP benefits while minimizing AFF risk. PMID: 30169557 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - September 2, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Coupling the circadian clock to homeostasis: the role of Period in timing physiology.
Authors: Kim P, Oster H, Lehnert H, Schmid SM, Salamat N, Barclay JL, Maronde E, Inder W, Rawashdeh O Abstract A plethora of physiological processes show stable and synchronized daily oscillations that are either driven or modulated by biological clocks. A circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the ventral hypothalamus coordinates 24-hour oscillations of central and peripheral physiology with the environment. The circadian clockwork involved in driving rhythmic physiology is composed of various clock genes that are interlocked via a complex feedback loop to generate precise yet plastic ...
Source: Endocrine Reviews - September 2, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Effects of anorexia nervosa on bone metabolism.
Authors: Fazeli PK, Klibanski A Abstract Anorexia nervosa is a psychiatric disease characterized by a low-weight state due to self-induced starvation. This disorder, which predominantly affects women, is associated with hormonal adaptations which minimize energy expenditure in the setting of low nutrient intake. These adaptations include growth hormone resistance, functional hypothalamic amenorrhea and non-thyroidal illness syndrome. Although these adaptations may be beneficial to short-term survival, they contribute to the significant and often persistent morbidity associated with this disorder, including bone los...
Source: Endocrine Reviews - September 1, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Structural and Functional Biology of Aldo-Keto Reductase Steroid Transforming Enzymes.
This article will review the crystal structures of these AKRs, their kinetic and catalytic mechanisms, AKR genomics (gene expression, splice variants, polymorphic variants, and inherited genetic deficiencies), distribution in steroid target tissues, roles in steroid hormone action and disease, and inhibitor design. PMID: 30137266 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - August 24, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment.
Authors: Vaidya A, Mulatero P, Baudrand R, Adler GK Abstract Primary aldosteronism is characterized by aldosterone secretion that is independent of renin and angiotensin II and sodium status. The deleterious effects of primary aldosteronism are mediated by excessive activation of the mineralocorticoid receptor that results in the well-known consequences of volume expansion, hypertension, hypokalemia, and metabolic alkalosis, but also increases the risk for cardiovascular and kidney disease, and death. For decades, the approaches to defining, diagnosing, and treating primary aldosteronism have been relatively consta...
Source: Endocrine Reviews - August 22, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Fibroblast Growth Factor 15/19 - From Basic Functions to Therapeutic Perspectives.
Authors: Emmanuel S, Jornayvaz FR Abstract Discovered 20 years ago, Fibroblast Growth Factor (FGF) 19, and its mouse ortholog FGF15, were the first members of a new subfamily of FGFs able to act as hormones. During fetal life, FGF15/19 is involved in organogenesis, affecting the development of the ear, eye, heart and brain. At adulthood, FGF15/19 is mainly produced by the ileum, acting on the liver to repress hepatic bile acid synthesis and promote postprandial nutrient partitioning. In rodents, pharmacologic doses of FGF19 induce the same anti-obesity and anti-diabetic actions as FGF21, these metabolic effects bei...
Source: Endocrine Reviews - August 22, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Obesity in Type 1 Diabetes: Pathophysiology, Clinical Impact and Mechanisms.
Authors: Corbin KD, Driscoll KA, Pratley RE, Smith SR, Maahs DM, Mayer-Davis EJ, Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON) Abstract There has been an alarming increase in the prevalence of obesity in people with type 1 diabetes in recent years. Although obesity has long been recognized as a major risk factor for the development of type 2 diabetes and a catalyst for complications, much less is known about the role of obesity in the initiation and pathogenesis of type 1 diabetes. Emerging evidence suggests that obesity contributes to insulin resistance, dyslipidemia and cardiometabolic complicat...
Source: Endocrine Reviews - July 31, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Molecular actions of PPAR α in lipid metabolism and inflammation.
Molecular actions of PPARα in lipid metabolism and inflammation. Endocr Rev. 2018 Jul 17;: Authors: Bougarne N, Weyers B, Desmet SJ, Deckers J, Ray DW, Staels B, De Bosscher K Abstract Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor of clinical interest as a drug target in various metabolic disorders. PPARα also exhibits marked anti-inflammatory capacities. The first generation PPARα agonists, the fibrates, have however been hampered by drug-drug interaction issues, statin drop-in and ill-designed cardiovascular intervention trials. Notwithstanding...
Source: Endocrine Reviews - July 20, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

The Biology of Normal Zona Glomerulosa And Aldosterone-Producing Adenoma: Pathological Implications.
Authors: Seccia TM, Caroccia B, Gomez-Sanchez EP, Gomez-Sanchez CE, Rossi GP Abstract The identification of several germline and somatic ion channel mutations in aldosterone-producing adenomas (APA) and detection of cell clusters that can be responsible for excess aldosterone production, as well as the isolation of autoantibodies activating the angiotensin II type 1 receptor, have rapidly advanced the understanding of the biology of primary aldosteronism (PA), in particular that of APA. Hence, the main purpose of this review is to discuss how discoveries of the last decade could impact on histopathology analysis an...
Source: Endocrine Reviews - July 15, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Interferences with thyroid function immunoassays: clinical implications and detection algorithm.
Authors: Favresse J, Burlacu MC, Maiter D, Gruson D Abstract Current automated immunoassays used to evaluate thyroid function are vulnerable to different types of interference that can impact clinical decision. This review provides a detailed overview of the six main interferences affecting measurements of thyroid-stimulating hormone, free thyroxine and free triiodothyronine, namely macroTSH, biotin, anti-streptavidin antibodies, anti-ruthenium antibodies, thyroid hormone autoantibodies, and heterophilic antibodies. As the prevalence of some of these conditions has been reported to approach 1% and the frequency of ...
Source: Endocrine Reviews - July 11, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Gonadotropins and their analogues: current and potential clinical applications.
Authors: Anderson RC, Newton CL, Anderson RA, Millar RP Abstract The gonadotropin receptors, luteinising hormone receptor, and follicle-stimulating hormone receptor, play a central role in governing reproductive competency/fertility. Gonadotropin hormone analogues have been utilised clinically for decades, in assisted reproductive therapies, and in the treatment of various infertility disorders. While these treatments are effective, the clinical protocols demand multiple injections, and the hormone preparations can lack uniformity and stability. The past two decades have seen a drive to develop chimeric and modifie...
Source: Endocrine Reviews - July 11, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Novel concepts for inducing final oocyte maturation in IVF (In Vitro Fertilization) Treatment.
Authors: Abbara A, Clarke SA, Dhillo WS Abstract Infertility affects 1 in 6 of the population and increasingly couples require treatment with assisted reproductive techniques (ART). In vitro fertilization (IVF) treatment is most commonly conducted using exogenous FSH to induce follicular growth and human chorionic gonadotrophin (hCG) to induce final oocyte maturation. However, hCG may cause the potentially life-threatening iatrogenic complication 'ovarian hyperstimulation syndrome' (OHSS), which can cause significant morbidity and rarely even mortality in otherwise healthy women. The use of GnRH agonists (GnRHa) ha...
Source: Endocrine Reviews - July 11, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Children born small for gestational age: differential diagnosis, molecular-genetic evaluation and implications.
Authors: Finken MJJ, van der Steen M, Smeets CCJ, Walenkamp MJE, de Bruin C, Hokken-Koelega ACS, Wit JM Abstract Children born small-for-gestational age (SGA), defined as a birth weight and/or length
Source: Endocrine Reviews - July 11, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Targeting the Incretin/Glucagon System with Triagonists to Treat Diabetes.
Authors: Capozzi ME, DiMarchi RD, Tschöp MH, Finan B, Campbell JE Abstract Glucagon-like peptide-1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of GLP-1R-directed strategies is sub-maximal, and the only potent, sustainable treatment for metabolic dysfunction is bariatric surgery, necessitating the development of novel therapeutics. GLP-1 is structurally related to glucagon and glucose-dependent insulinotropic peptide (GIP), allowing for the development of intermixed, unimolecular pep...
Source: Endocrine Reviews - June 17, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Two hormones for one receptor: evolution, biochemistry, actions and pathophysiology of LH and hCG.
Authors: Casarini L, Santi D, Brigante G, Simoni M Abstract Luteinizing hormone (LH) and chorionic gonadotropin (CG) are glycoproteins fundamental for sexual development and reproduction. Since they act on the same receptor (LHCGR), there is a general consensus that LH and hCG are equivalent. However, separate evolution of LHβ and hCGβ subunits occurred in primates, resulting in two molecules sharing ∼85% identity and regulating different physiological events. Pituitary, pulsatile LH production results in a ∼90 min half-life molecule targeting the gonads, to regulate gametogenesis and androgen syn...
Source: Endocrine Reviews - June 17, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy.
Authors: Hardy RS, Zhou H, Seibel MJ, Cooper MS Abstract Osteoporosis associated with long-term glucocorticoid therapy remains a common and serious bone disease. In addition, in recent years it has become clear that more subtle states of endogenous glucocorticoid excess may have a major impact on bone health. Adverse effects can be seen with mild systemic glucocorticoid excess but there is also evidence of tissue-specific regulation of glucocorticoid action within bone as a mechanism of disease. This review article will examine a) the role of endogenous glucocorticoids in normal bone physiology, b) the skeletal eff...
Source: Endocrine Reviews - June 17, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Estrogen Receptors: New Directions in the New Millennium.
Authors: Hewitt SC, Korach KS Abstract Nineteen years have passed since our previous review in this journal in 1999 regarding estrogen receptors. At that time, we described the current assessments of the physiological activities of estrogen and ER. Since that time there has been an explosion of progress in our understanding of details of estrogen receptor mediated processes from the molecular and cellular level to the whole organism. Here, we will review the basic understanding of estrogen signaling, then elaborate on the progress and current understanding of estrogen receptor actions that have developed using new ...
Source: Endocrine Reviews - June 16, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Regulation of Skeletal Homeostasis.
Authors: Zaidi M, Yuen T, Sun L, Rosen CJ Abstract Landmark advances in skeletal biology have arisen mainly from the identification of disease-causing mutations and the advent of rapid and selective gene targeting technologies to phenocopy human disease in mice. Here, we discuss work on newly identified mechanisms controlling the remodeling of bone, communication of bone cells with cells of other lineages, and crosstalk between bone and vital organs, as these relate to the therapeutic targeting of the skeleton. PMID: 29897433 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - June 14, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

At the crossroads of fate - somatic cell lineage specification in the fetal gonad.
Authors: Rotgers E, Jørgensen A, Yao HH Abstract The reproductive endocrine systems are vastly different between male and female. This sexual dimorphism of endocrine milieu originates from sex-specific differentiation of the somatic cells in the gonads during fetal life. The majority of gonadal somatic cells arise from the adrenogonadal primordium. After separation of the adrenal and gonadal primordia, the gonadal somatic cells initiate sex-specific differentiation during gonadal sex determination with the specification of the supporting cell lineages: Sertoli cells in the testis vs. granulosa cells in the o...
Source: Endocrine Reviews - May 18, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Metabolic flexibility as an adaptation to energy resources and requirements in health and disease.
Authors: Smith RL, Soeters MR, Wüst RCI, Houtkooper RH Abstract The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue and muscle govern systemic metaboli...
Source: Endocrine Reviews - April 28, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Pituitary Diseases and Bone.
Authors: Mazziotti G, Frara S, Giustina A Abstract Neuroendocrinology of bone is a new area of research based on the evidence that pituitary hormones may directly modulate bone remodeling and metabolism. Skeletal fragility associated with high risk of fractures is a common complication of several pituitary diseases such as hypopituitarism, Cushing disease, acromegaly and hyperprolactinemia. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity and fractures may occur even in the presence of normal or low-normal bone mineral density as measured by dual-...
Source: Endocrine Reviews - April 25, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research

Sex and Gender Differences Research Design for Basic, Clinical and Population Studies: Essentials for Investigators.
Authors: Rich-Edwards JW, Kaiser UB, Chen GL, Manson JE, Goldstein J Abstract A sex and gender-informed perspective increases rigor, promotes discovery, and expands the relevance of biomedical research. In the current era of accountability to present data for males and females, thoughtful and deliberate methodology can improve study design and inference in sex and gender differences research. We address issues of motivation, subject selection, sample size, data collection, analysis, and interpretation, considering implications for basic, clinical, and population research. In particular, we focus on methods to test ...
Source: Endocrine Reviews - April 19, 2018 Category: Endocrinology Tags: Endocr Rev Source Type: research