John T Walker, Diane C Saunders, Marcela Brissova, Alvin C Powers
This review focuses on the human pancreatic islet - including its structure, cell composition, development, function, and dysfunction. After providing a historical timeline of key discoveries about human islets over the past century, we describe new research approaches and technologies that are being used to study human islets and how these are providing insight into human islet physiology and pathophysiology. We also describe changes or adaptations in human islets in response to physiologic challenges such as pregnancy, aging, and insulin resistance and discuss islet changes in human diabetes of many forms...
April 12, 2021: Endocrine Reviews
Robert L Rosenfield
Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to ACTH that are best indexed by dehydroepiandrosterone sulfate (DHEAS) rise. These changes are related to the development of the zona reticularis (ZR) and its unique gene/enzyme expression pattern of low 3ß-hydroxysteroid dehydrogenase type 2 with high cytochrome b5A, sulfotransferase 2A1, and 17ß-hydroxysteroid dehydrogenase type 5. Recently 11-ketotestosterone was identified as an important bioactive adrenarchal androgen...
March 31, 2021: Endocrine Reviews
Priska Stahel, Changing Xiao, Avital Nahmias, Lili Tian, Gary Franklin Lewis
Plasma triglyceride-rich lipoproteins (TRL), particularly atherogenic remnant lipoproteins, contribute to atherosclerotic cardiovascular disease (ASCVD). Hypertriglyceridemia may arise in part from hypersecretion of TRLs by the liver and intestine. Here we focus on the complex network of hormonal, nutritional, and neuronal interorgan communication that regulates secretion of TRLs, and provide our perspective on the relative importance of these factors. Hormones and peptides originating from the pancreas (insulin, glucagon), gut (GLP-1, GLP-2, ghrelin, CCK, peptide YY), adipose tissue (leptin, adiponectin) and brain (GLP-1) modulate TRL secretion by receptor-mediated responses and indirectly via neural networks...
March 20, 2021: Endocrine Reviews
Sebastian Schneeweiss, Elisabetta Patorno
Real-world Evidence (RWE), the understanding of treatment effectiveness in clinical practice generated from longitudinal patient-level data from the routine operation of the healthcare system, is thought to complement evidence on the efficacy of medications from RCTs. RWE studies follow a structured approach: (1) A design layer decides on the study design, which is driven by the study question and refined by a medically informed target population, patient-informed outcomes, and biologically informed effect windows...
March 12, 2021: Endocrine Reviews
Aditi Bhargava, Arthur P Arnold, Debra A Bangasser, Kate M Denton, Arpana Gupta, Lucinda M Hilliard Krause, Emeran A Mayer, Margaret McCarthy, Walter L Miller, Armin Raznahan, Ragini Verma
In May 2014, the National Institutes of Health (NIH) stated its intent to "require applicants to consider sex as a biological variable (SABV) in the design and analysis of NIH-funded research involving animals and cells." Since then, proposed research plans that include animals routinely state that both sexes/genders will be used; however, in many instances, researchers and reviewers are at a loss about the issue of sex differences. Moreover, the terms sex and gender are used interchangeably by many researchers, further complicating the issue...
March 11, 2021: Endocrine Reviews
Amir Ajoolabady, Shuyi Wang, Guido Kroemer, Daniel J Klionsky, Vladimir N Uversky, James R Sowers, Hamid Aslkhodapasandhokmabad, Yaguang Bi, Junbo Ge, Jun Ren
The endoplasmic reticulum (ER) hosts linear polypeptides and fosters natural folding of proteins through ER-residing chaperones and enzymes. Failure of the ER to align and compose proper protein architecture leads to accumulation of misfolded/unfolded proteins in the ER lumen, which disturbs ER homeostasis to provoke ER stress. Presence of ER stress initiates the cytoprotective unfolded protein response (UPR) to restore ER homeostasis or instigates a rather maladaptive UPR to promote cell death. Although a wide array of cellular processes such as persistent autophagy, dysregulated mitophagy, and secretion of pro-inflammatory cytokines may contribute to the onset and progression of cardiometabolic diseases, it is well perceived that ER stress also evokes onset and development of cardiometabolic diseases, particularly, cardiovascular diseases, diabetes mellitus, obesity, and chronic kidney disease...
March 8, 2021: Endocrine Reviews
T John Martin, Natalie A Sims, Ego Seeman
The hormone, parathyroid hormone (PTH) and the paracrine factor, parathyroid hormone-related protein (PTHrP) have preserved in evolution sufficient identities in their amino-terminal domains to share equivalent actions upon a common G protein coupled receptor, PTH1R, that predominantly uses the cyclic AMP (cAMP)-protein kinase A signaling pathway. Such a relationship between a hormone and local factor poses questions about how their common receptor mediates pharmacological and physiological actions of the two...
February 10, 2021: Endocrine Reviews
Adil Rasheed, Katey J Rayner
Work over the last 40 years have described macrophages as a heterogeneous population that serve as the frontline surveyors of tissue immunity. As a class, macrophages are found in almost every tissue in the body and as distinct populations within discrete microenvironments in any given tissue. During homeostasis, macrophages protect these tissues by clearing invading foreign bodies and/or mounting immune responses. In addition to varying identities regulated by transcriptional programs shaped by their respective environments, macrophage metabolism serves as an additional regulator to temper responses to extracellular stimuli...
February 1, 2021: Endocrine Reviews
Steffen Maak, Frode Norheim, Christian A Drevon, Harold P Erickson
In 2002, a transmembrane protein now known as FNDC5 was discovered and shown to be expressed in skeletal muscle, heart and brain. It was virtually ignored for 10 years, until a study in 2012 proposed that, in response to exercise, the ectodomain of skeletal muscle FNDC5 was cleaved,traveled to white adipose tissue and induced browning. The wasted energy of this browning raised the possibility that this myokine, named irisin, might mediate some beneficial effects of exercise. Since then, more than 1,000 papers have been published exploring the roles of irisin...
January 25, 2021: Endocrine Reviews
David J Handelsman
Androgens are potent drugs requiring prescription for valid medical indications but are misused for invalid, unproven, or off-label reasons as well as being abused without prescription for illicit non-medical application for performance or image enhancement. Following discovery and first clinical application of testosterone in the 1930s, commercialisation of testosterone and synthetic androgens proliferated in the decades after World War II. It remains among the oldest marketed drugs in therapeutic use, yet after 8 decades of clinical use the sole unequivocal indication for testosterone remains in replacement therapy for pathological hypogonadism, organic disorders of the male reproductive system...
January 23, 2021: Endocrine Reviews
Kunal Desai, Jeff McManus, Nima Sharifi
Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement, from the types of gonadal testosterone deprivation, to modalities that block the generation of adrenal and other extragonadal androgens, to those that directly bind and inhibit the androgen receptor (AR). The clinical states of prostate cancer are the product of a superimposition of these therapies with non-metastatic advanced prostate cancer, as well as frankly metastatic disease...
January 22, 2021: Endocrine Reviews
Sandra Pereira, Daemon L Cline, Maria M Glavas, Scott D Covey, Timothy J Kieffer
The discovery of leptin was intrinsically associated with its ability to regulate body weight. However, the effects of leptin are more far-reaching and include profound glucose-lowering and anti-lipogenic effects, independent of leptin's regulation of body weight. Regulation of glucose metabolism by leptin is mediated both centrally and via peripheral tissues and is influenced by the activation status of insulin signaling pathways. Ectopic fat accumulation is diminished by both central and peripheral leptin, an effect that is beneficial in obesity-associated disorders...
January 28, 2021: Endocrine Reviews
Vasantha Padmanabhan, Wenhui Song, Muraly Puttabyatappa
The burden of adverse pregnancy outcomes such as preterm birth and low birth weight is considerable across the world. Several risk factors for adverse pregnancy outcomes have been identified. One risk factor for adverse pregnancy outcomes that is receiving considerable attention in recent years is gestational exposure to endocrine disrupting chemicals (EDCs). Humans are exposed to multitude of environmental chemicals with known endocrine disrupting properties and evidence suggest that exposure to these EDCs have the potential to disrupt maternal-fetal environment culminating in adverse pregnancy and birth outcomes...
January 3, 2021: Endocrine Reviews
Manita Shakya, Iris Lindberg
The kexin-like proprotein convertases perform the initial proteolytic cleavages that ultimately generate a variety of different mature peptide and proteins, ranging from brain neuropeptides, to endocrine peptide hormones, to structural proteins, among others. In this review, we present a general introduction to proprotein convertase structure and biochemistry, followed by a comprehensive discussion of each member of the kexin-like subfamily of proprotein convertases. We summarize current knowledge of human proprotein convertase insufficiency syndromes, including genome-wide analyses of convertase polymorphisms, and compare these to convertase null and mutant mouse models...
December 31, 2020: Endocrine Reviews
Arthur D Riggs
In the mid to late 1970s recombinant DNA methods for cloning and expressing genes in E. coli were under intense development. An important question had become: Can humans design and chemically synthesize novel genes that function in bacteria? This question was answered in 1978 and 1979 with the successful expression in E. coli of two mammalian hormones, first somatostatin and then human insulin. The successful production of human insulin in bacteria provided, for the first time, a practical, scalable source of human insulin and resulted in the approval, in 1982, of human insulin for the treatment of diabetics...
December 19, 2020: Endocrine Reviews
Brent A McLean, Chi Kin Wong, Jonathan E Campbell, David J Hodson, Stefan Trapp, Daniel J Drucker
Glucagon-like peptide-1 (GLP-1) is produced in gut endocrine cells and in the brain, and acts through hormonal and neural pathways to regulate islet function, satiety, and gut motility, supporting development of GLP-1 receptor (GLP-1R) agonists for the treatment of diabetes and obesity. Classic notions of GLP-1 acting as a meal-stimulated hormone from the distal gut are challenged by data supporting production of GLP-1 in the endocrine pancreas, and by the importance of brain-derived GLP-1 in the control of neural activity...
December 15, 2020: Endocrine Reviews
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December 1, 2020: Endocrine Reviews
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December 1, 2020: Endocrine Reviews
Johanne Grosbois, Melody Devos, Isabelle Demeestere
In recent years, ovarian tissue cryopreservation has rapidly developed as a successful method for preserving the fertility of girls and young women with cancer or benign conditions requiring gonadotoxic therapy, and is now becoming widely recognized as an effective alternative to oocyte and embryo freezing when not feasible. Primordial follicles are the most abundant population of follicles in the ovary, and their relatively quiescent metabolism makes them more resistant to cryoinjury. This dormant pool represents a key target for fertility preservation strategies as a resource for generating high-quality oocytes...
December 1, 2020: Endocrine Reviews
Vinaya Srirangam Nadhamuni, Márta Korbonits
Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or nonsyndromic conditions with pituitary tumor predisposition. These include the identification of novel germline variants in patients with familial or simplex pituitary tumors and establishment of novel somatic variants identified through next generation sequencing. Advanced techniques have allowed the exploration of epigenetic mechanisms mediated through DNA methylation, histone modifications and noncoding RNAs, such as microRNA, long noncoding RNAs and circular RNAs...
December 1, 2020: Endocrine Reviews
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