ERRATUM FOR "Delayed Puberty-Phenotypic Diversity, Molecular Genetic Mechanisms, and Recent Discoveries".
ERRATUM FOR "Delayed Puberty-Phenotypic Diversity, Molecular Genetic Mechanisms, and Recent Discoveries". Endocr Rev. 2020 Jan 11;: Authors: PMID: 31926007 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - January 12, 2020 Category: Endocrinology Tags: Endocr Rev Source Type: research

Metabolic Effects of Oxytocin.
Authors: McCormack SE, Blevins JE, Lawson EA Abstract There is growing evidence that oxytocin (OXT), a hypothalamic hormone well recognized for its effects in inducing parturition and lactation, has important metabolic effects in both sexes. The purpose of this review is to summarize the physiologic effects of OXT on metabolism and to explore its therapeutic potential for metabolic disorders. In model systems, OXT promotes weight loss by decreasing energy intake. Pair-feeding studies suggest that OXT-induced weight loss may also be partly due to increased energy expenditure and/or lipolysis. In humans, OXT appears ...
Source: Endocrine Reviews - December 6, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Leptin - is it thermogenic?
Authors: Fischer AW, Cannon B, Nedergaard J Abstract Animals that lack the hormone leptin become grossly obese, purportedly for two reasons: increased food intake and decreased energy expenditure (thermogenesis). This review examines the experimental evidence for the thermogenesis component. Analysis of the data available lead us to conclude that the reports indicating hypometabolism in the leptin-deficient ob/ob mice (as well as in the leptin-receptor-deficient db/db mice and fa/fa rats) derive from a misleading calculation artefact resulting from expression of energy expenditure per g body weight and not per inta...
Source: Endocrine Reviews - November 29, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Thyroid hormone transporters.
Authors: Groeneweg S, van Geest FS, Peeters RP, Heuer H, Visser WE Abstract Thyroid hormone transporters at the plasma membrane govern intracellular bioavailability of thyroid hormone. Monocarboxylate transporters (MCT) 8 and MCT10, organic anion transporting polypeptide (OATP) 1C1 and SLC17A4 are currently known as transporters displaying highest specificity towards thyroid hormones. Structure-function studies using homology modelling and mutational screens have led to better understanding of the molecular basis of thyroid hormone transport. Mutations in MCT8 and in OATP1C1 have been associated with clinical disor...
Source: Endocrine Reviews - November 23, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Review: Diabetes, Obesity and Cancer - Pathophysiology and Clinical Implications.
Authors: Lega IC, Lipscombe LL Abstract Obesity and diabetes have both been associated with an increased risk of cancer. In the face of increasing obesity and diabetes rates worldwide, this is a worrying trend for cancer rates. Factors such as hyperinsulinemia, chronic inflammation, anti-hyperglycemic medications and shared risk factors have all been identified as potential mechanisms underlying the relationship. The most common obesity- and diabetes-related cancers are endometrial, colorectal and post menopausal breast cancers. In this review, we summarize the existing evidence that describes the complex relations...
Source: Endocrine Reviews - November 15, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

The new biology of diabetic kidney disease - mechanisms and therapeutic implications.
Authors: Lytvyn Y, Bjornstad P, van Raalte DH, Heerspink HL, Cherney DZI Abstract Diabetic kidney disease remains the most common cause of end-stage kidney disease in the world. Despite reductions in incidence rates of myocardial infarction and stroke in people with diabetes over the past 3 decades, the risk of diabetic kidney disease has remained unchanged, and may even be increasing in younger individuals afflicted with this disease. Accordingly, changes in public health policy have to be implemented to address the root causes of diabetic kidney disease, including the rise of obesity and diabetes, in addition to ...
Source: Endocrine Reviews - October 23, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Brown adipose cross talk in tissue plasticity and human metabolism.
Authors: Scheele C, Wolfrum C Abstract Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increase metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and include secretion of factors, known as batokines, which target several different cell types within the BAT, and promote adipogenesis, angiogenesis, immune cell interactions and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies ha...
Source: Endocrine Reviews - October 23, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Non-alcoholic fatty liver disease in adults: Current concepts in etiology, outcomes and management.
Authors: Marjot T, Moolla A, Cobbold JF, Hodson L, Tomlinson JW Abstract Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease, extending from simple steatosis, through to inflammation and fibrosis with a significant risk for the development of cirrhosis. It is highly prevalent and is associated with significant adverse outcomes both through liver-specific morbidity and mortality, but perhaps more importantly, through adverse cardiovascular and metabolic outcomes. It is tightly associated with type 2 diabetes and obesity and both of these conditions drive progressive disease towards the more advanced s...
Source: Endocrine Reviews - October 20, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Advances in the diagnosis and management of well-differentiated neuroendocrine neoplasms.
Authors: Hofland J, Kaltsas G, de Herder WW Abstract Neuroendocrine neoplasms (NENs) constitute a diverse group of tumors that derive from the sensory and secretory neuroendocrine cells and predominantly arise within the pulmonary and gastrointestinal tracts. The majority of these neoplasms have a well-differentiated grade and are termed neuroendocrine tumors (NETs). This subgroup is characterized by limited proliferation and patients affected by these tumors carry a good to moderate prognosis. A substantial subset of patients presenting with a NET suffer from the consequences of endocrine syndromes due to the exce...
Source: Endocrine Reviews - September 27, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

The role of sex and sex Hormones in Neurodegenerative Diseases.
Authors: Vegeto E, Villa A, Della Torre S, Crippa V, Rusmini P, Cristofani R, Galbiati M, Maggi A, Poletti A Abstract Neurodegenerative diseases (NDs) are a wide class of disorders of the central nervous system (CNS) with still unknown etiology. Several factors were hypothesized to be involved in the pathogenesis of these diseases including genetic and environmental factors. Many of these diseases show a sex prevalence and sex steroids where shown to have a role in the progression of specific forms of neurodegeneration. Estrogens were reported to be neuroprotective though their action on cognate nuclear and membran...
Source: Endocrine Reviews - September 24, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Glucose-Dependent Insulinotropic Polypeptide Receptor Therapies For The Treatment Of Obesity, Do Agonists = Antagonists?
Authors: Killion EA, Lu SC, Fort M, Yamada Y, Véniant MM, Lloyd DJ Abstract Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) is associated with obesity in human genome-wide association studies (GWAS). Similarly, mouse genetic studies indicate that loss of function alleles and GIP overexpression both protect from high-fat diet (HFD)-induced weight gain. Together, these data provide compelling evidence to develop therapies targeting GIPR for the treatment of obesity. Further, both antagonists and agonists alone prevent weight gain, but result in remarkable weight loss when co-dosed or molecul...
Source: Endocrine Reviews - September 13, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Glucose-Dependent Insulinotropic Polypeptide Receptor Therapies For The Treatment Of Obesity, Do Agonists = Antagonists?
Authors: Killion EA, Lu SC, Fort M, Yamada Y, Véniant MM, Lloyd DJ Abstract Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) is associated with obesity in human genome-wide association studies (GWAS). Similarly, mouse genetic studies indicate that loss of function alleles and GIP overexpression both protect from high-fat diet (HFD)-induced weight gain. Together, these data provide compelling evidence to develop therapies targeting GIPR for the treatment of obesity. Further, both antagonists and agonists alone prevent weight gain, but result in remarkable weight loss when co-dosed or molecul...
Source: Endocrine Reviews - September 13, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Progesterone and breast cancer.
Authors: Trabert B, Sherman ME, Kannan N, Stanczyk FZ Abstract Synthetic progestogens (progestins) have been linked to increased breast cancer risk; however, the role of endogenous progesterone in breast physiology and carcinogenesis is less clearly defined. Mechanistic studies using cell culture, tissue culture, and preclinical models implicate progesterone in breast carcinogenesis. In contrast, limited epidemiologic data generally do not show an association of circulating progesterone levels with risk, and it is unclear whether this reflects methodologic limitations or a truly null relationship. Challenges relate...
Source: Endocrine Reviews - September 13, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Autoimmune pituitary disease: New concepts with clinical implications.
Authors: Yamamoto M, Iguchi G, Bando H, Kanie K, Hidaka-Takeno R, Fukuoka H, Takahashi Y Abstract Some endocrine disorders, including hypophysitis and isolated ACTH deficiency, are caused by an autoimmune response to endocrine organs. Although the pathogenesis of some autoimmune endocrine diseases has been elucidated, it remains obscure for most. Anti-PIT-1 hypophysitis (anti-PIT-1 antibody syndrome) is a newly described pituitary autoimmune disease characterized by acquired and specific growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiencies. This disorder is associated with a thym...
Source: Endocrine Reviews - September 13, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Management of 46,XY Differences/Disorders of Sex Development (DSD) Throughout Life.
Authors: Wisniewski AB, Batista RL, Costa EMF, Finlayson C, Sircili MHP, Dénes FT, Domenice S, Mendonca BB Abstract Differences/Disorders of sex development (DSD) are a heterogeneous group of congenital conditions that result in discordance between an individual's sex chromosomes, gonads, and/or anatomic sex. Advances in the clinical care of patients and families affected by 46,XY DSD have been achieved since publication of the original Consensus meeting in 2006. The aims of this paper are to review what is known about morbidity and mortality, diagnostic tools and timing, sex of rearing, endocrine and surgic...
Source: Endocrine Reviews - August 1, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond.
Authors: Cabanillas ME, Ryder M, Jimenez C Abstract The treatment of advanced thyroid cancer has undergone rapid evolution in the past decade, with multiple kinase inhibitor drug approvals for each subtype of thyroid cancer and a number of other commercially available drugs that have been studied for this indication. While most of the FDA approved drugs are anti-angiogenic multikinase inhibitors-vandetanib, cabozantinib, sorafenib, lenvatinib-there are two FDA indications that are mutation specific-dabrafenib/trametinib for BRAF mutated anaplastic thyroid cancer and larotrectinib for NTRK fusion thyroid cancer. Fur...
Source: Endocrine Reviews - July 21, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Genetic risk scores for diabetes diagnosis and precision medicine.
Authors: Udler MS, McCarthy MI, Florez JC, Mahajan A Abstract Over the last decade, there have been substantial advances in the identification and characterization of DNA sequence variants associated with individual predisposition to type 1 and type 2 diabetes. As well as providing insights into the molecular, cellular and physiological mechanisms involved in disease pathogenesis, these risk variants, when combined into a polygenic score, capture information on individual patterns of disease predisposition that have the potential to influence clinical management. In this review, we describe the various opportunitie...
Source: Endocrine Reviews - July 21, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Contemporary debates in adult papillary thyroid cancer management.
Authors: McLeod DSA, Zhang L, Durante C, Cooper DS Abstract An ever-increasing population of patients with differentiated thyroid cancer is engaging with healthcare systems around the world. Numerous questions about optimal management have arisen that challenge conventional paradigms. This is particularly the case for patients with low-risk disease, which comprise the majority of new patients. At the same time, new therapies for patients with advanced disease all are also being introduced, which may have the potential to prolong life. This review discusses selected controversial issues in adult papillary thyroid ca...
Source: Endocrine Reviews - July 21, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Steroid metabolome analysis in disorders of adrenal steroid biosynthesis and metabolism.
Authors: Storbeck KH, Schiffer L, Baranowski ES, Chortis V, Prete A, Barnard L, Gilligan LC, Taylor AE, Idkowiak J, Arlt W, Shackleton CHL Abstract Steroid biosynthesis and metabolism is reflected by the serum steroid metabolome and, in even more detail, by the 24-hour urine steroid metabolome, which can provide unique insights into alterations of steroid flow and output indicative of underlying conditions. Mass spectrometry-based steroid metabolome profiling has allowed for the identification of unique multi-steroid signatures associated with disorders of steroid biosynthesis and metabolism that can be used for pe...
Source: Endocrine Reviews - July 12, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Realizing a Closed-Loop (Artificial Pancreas) System for the Treatment of Type 1 Diabetes.
Authors: Lal RA, Ekhlaspour L, Hood K, Buckingham B Abstract Recent, rapid changes in the treatment of type 1 diabetes have allowed for commercialization of an "artificial pancreas" which is better described as a closed-loop controller of insulin delivery. This review presents the current state of closed-loop control systems and expected future developments with a discussion of the human factor issues in allowing automation of glucose control. The goal of these systems is to minimize or prevent both short and long-term complications from diabetes and to decrease the daily burden of managing diabetes. The ...
Source: Endocrine Reviews - July 7, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

The effects of bariatric surgery on islet function, insulin secretion, & glucose control.
This article is based on literature related to factors governing glucose metabolism and insulin secretion after the commonly used RYGB and VSG, and the less frequently used BPD and adjustable gastric banding. PMID: 31241742 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - June 28, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Delayed Puberty - Phenotypic Diversity, Molecular Genetic Mechanisms and Recent Discoveries.
Authors: Howard SR, Dunkel L Abstract This review presents a comprehensive discussion of the clinical condition of delayed puberty, a common presentation to the paediatric endocrinologist, which may present both diagnostic and prognostic challenges. Our understanding of the genetic control of pubertal timing has advanced thanks to active investigation in this field over the last two decades, but remains in large part a fascinating and mysterious conundrum. The phenotype of delayed puberty is associated with adult health risks and common etiologies, and there is evidence for polygenic control of pubertal timing in t...
Source: Endocrine Reviews - June 22, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

CORRIGENDUM FOR "Growth Hormone's Links to Cancer".
CORRIGENDUM FOR "Growth Hormone's Links to Cancer". Endocr Rev. 2019 Jun 07;: Authors: PMID: 31173080 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - June 8, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Inflammation in the pathophysiology and therapy of cardiometabolic disease.
Authors: Donath MY, Meier DT, Böni-Schnetzler M Abstract The role of chronic inflammation in the pathogenesis of type 2 diabetes mellitus and associated complications is now well established. Therapeutic interventions counteracting metabolic inflammation improve insulin secretion and action, glucose control, and may prevent long-term complications. Thus, a number of anti-inflammatory drugs approved for the treatment of other inflammatory conditions are evaluated in patients with metabolic syndrome. Most advanced are clinical studies with interleukin-1 antagonists showing improved β-cell function and glyca...
Source: Endocrine Reviews - May 29, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Bone Marrow Adiposity: Basic and Clinical Implications.
Authors: Sebo ZL, Rendina-Ruedy E, Ables GP, Lindskog DM, Rodeheffer MS, Fazeli PK, Horowitz MC Abstract The presence of adipocytes in mammalian bone marrow (BM) has been recognized histologically for decades, yet, until recently, these cells have received little attention from the research community. Advancements in mouse transgenics and imaging methods, particularly in the last ten years, have permitted more detailed examinations of marrow adipocytes than ever before and yielded data that show these cells are critical regulators of the BM microenvironment and whole body metabolism. Indeed, marrow adipocytes are a...
Source: Endocrine Reviews - May 29, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

The liver as an endocrine organ - linking NAFLD and insulin resistance.
We describe the NAFLD-induced changes in secretion of liver proteins, lipids, other metabolites, and miRNAs, and how these molecules alter metabolism in liver, muscle, adipose tissue and pancreas to induce insulin resistance. We also synthesise the limited information which indicates that extracellular vesicles, and in particular exosomes, may be an important mechanism for inter-tissue communication in normal physiology and in promoting metabolic dysregulation in NAFLD. PMID: 31098621 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - May 19, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Diabetic gastroparesis.
DIABETIC GASTROPARESIS. Endocr Rev. 2019 May 13;: Authors: Bharucha AE, Kudva YC, Prichard DO Abstract This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus (DM). Up to 50% of patients with type 1 and 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13 C-breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many p...
Source: Endocrine Reviews - May 15, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

The gut microbiome influences host endocrine functions.
In conclusion, this review summarizes recent state-of-the art aiming at providing evidence that the gut microbiome influences host endocrine functions via several bacterial-derived metabolites. PMID: 31081896 [PubMed - as supplied by publisher] (Source: Endocrine Reviews)
Source: Endocrine Reviews - May 15, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Clinical guidelines and PTH measurement: does assay generation matter?
Authors: Smit MA, van Kinschot CMJ, van der Linden J, van Noord C, Kos S Abstract Parathyroid hormone (PTH) is an important regulator of calcium and phosphate homeostasis and bone remodeling. PTH is metabolized into PTH fragments which are measured to a different extent by PTH assays of different generations. This is due to differences in fragments recognized and lack of assay standardization. PTH is measured in the workup of several conditions and clinical guidelines provide recommendations concerning these measurements. This review provides an overview of the impact of differences between PTH assays, when applyin...
Source: Endocrine Reviews - May 15, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

The role of sexual hormones on the entero-insular axis.
Authors: Handgraaf S, Philippe J Abstract Sex steroid estrogens, androgens, and progesterone, produced by the gonads which have long been considered as endocrine glands, are implicated in sexual differentiation, puberty, and reproduction. However, the impact of sexual hormones goes beyond these effects through their role on energy metabolism. Indeed, sexual hormones are important physiological regulators of glucose homeostasis and, in particular of the entero-insular axis. In this review, we describe the roles of estrogens, androgens, and progesterone on glucose homeostasis, through their effects on pancreatic alph...
Source: Endocrine Reviews - May 12, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

The Aging Thyroid: A Reappraisal Within the Geroscience Integrated Perspective.
Authors: Franceschi C, Ostan R, Mariotti S, Monti D, Vitale G Abstract Thyroid plays a crucial and pervasive role in physiology (metabolism, thermogenesis and immunity, among others) and its aging and related changes in thyroid hormones production contribute to the common occurrence of thyroid diseases in elderly and to age-associated changes in other organs and systems. We address the complexity of thyroid aging following the basic suggestions of Geroscience. This integrative new perspective identifies few basic molecular mechanisms or "pillars" (inflammation, adaptation to stress, loss of proteostasis, ...
Source: Endocrine Reviews - May 12, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Potential clinical error arising from use of HbA1c in diabetes: effects of the Glycation Gap.
Authors: Nayak AU, Singh BM, Dunmore SJ Abstract The Glycation Gap (GGap) and the similar Hemoglobin Glycation Index (HGI) define consistent differences between glycated hemoglobin and actual glycemia derived from fructosamine or mean blood glucose respectively. Such a disparity may be found in a substantial proportion of people with diabetes, being> than 1 unit of glycated HbA1c% or 7.2 mmol/mol in almost 40% of estimations. In this review we define these indices, explain how they can be calculated and that they are not spurious, being consistent in individuals over time. We evaluate the evidence that GGap and ...
Source: Endocrine Reviews - May 12, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Uterine Glands: Developmental Biology and Functional Roles in Pregnancy.
Authors: Kelleher AM, DeMayo FJ, Spencer TE Abstract All mammalian uteri contain glands in the endometrium that develop only or primarily after birth. Gland development or adenogenesis in the postnatal uterus is intrinsically regulated by proliferation, cell-cell interactions, growth factors and their inhibitors as well as transcription factors including forkhead box A2 (FOXA2) and estrogen receptor alpha (ESR1). Extrinsic factors regulating adenogenesis originate from other organs including the ovary, pituitary, and mammary gland. The infertility and recurrent pregnancy loss observed in uterine gland knockout shee...
Source: Endocrine Reviews - May 12, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Insulin Resistance and Atherosclerosis: Implications for Insulin Sensitizing Agents.
Authors: Di Pino A, DeFronzo RA Abstract Type 2 diabetic patients are at high risk for macrovascular complications, which represent the major cause of mortality. Despite effective treatment of established cardiovascular (CV) risk factors (dyslipidemia, hypertension, procoagulant state), there remains a significant amount of unexplained cardiovascular risk. Insulin resistance is associated with a cluster of cardiometabolic risk factors known collectively as the insulin resistance (metabolic) syndrome (IRS). Considerable evidence, reviewed herein, suggests that insulin resistance and the IRS contribute to this unexpl...
Source: Endocrine Reviews - May 6, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Paradigms of Dynamic Control of Thyroid Hormone Signaling.
Authors: Bianco AC, Dumitrescu A, Gereben B, Ribeiro MO, Fonseca TL, Fernandes GW, Bocco BMLC Abstract Thyroid hormone (TH) molecules enter cells via membrane transporters and, depending on the cell type, can be activated, that is thyroxine (T4) to 3,5,3'-tri-iodothyronine (T3) conversion, or inactivated - T3 to 3,3'-diiodo-L-thyronine (T2) or T4 to reverse tri-iodothyronine (rT3) conversion. These reactions are catalyzed by the deiodinases. The biologically active hormone, T3, eventually binds to intracellular TH receptors (TR), TRα and TRβ, and initiate TH signaling, i.e. regulation of target genes and...
Source: Endocrine Reviews - May 1, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

Endometriosis.
Authors: Bulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S, Kohlmeier A, Yin P, Milad M, Wei J Abstract Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extra-uterine endometriotic tissue involve defectively progr...
Source: Endocrine Reviews - April 19, 2019 Category: Endocrinology Tags: Endocr Rev Source Type: research

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