Endocrine Reviews

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 applying distinct clinical guidelines for primary and secondary hyperparathyroidism and perioperative use of PTH measurements...

The gut microbiome is now considered as an organ contributing to the regulation of host metabolism. Since the finding of the existence of a relationship between the gut microbiome and specific diseases, numerous studies have also deciphered molecular mechanisms explaining how gut bacteria dialogue with host cells and eventually shape metabolism. Both metagenomic and metabolomic analyses have contributed to the discovery of bacterial-derived metabolites acting on host cells. In this review, we examine the molecular mechanisms by which bacterial metabolites are acting as paracrine or endocrine factors thereby regulating host metabolism...

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 patients with delayed GE are asymptomatic; others have dyspepsia (i...

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 sheep and mouse models support a primary role for secretions and products of the glands in pregnancy success...

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...

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, stem cell exhaustion, metabolism derangement, macromolecular damage, and epigenetic modifications) as a unifying conceptual framework to understand the aging process and age-associated diseases...

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 alpha and beta-cells as well as on entero-endocrine L-cells and their implication in hormonal biosynthesis and secretion...

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 unexplained cardiovascular risk in type 2 diabetic patients...

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 other metabolic pathways...

The liver is a dynamic organ that plays critical roles in many physiological processes, including the regulation of systemic glucose and lipid metabolism. Dysfunctional hepatic lipid metabolism is a cause of non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. Through the use of advanced mass spectrometry 'omics' approaches and detailed experimentation in cells, mice and humans, we now understand that the liver secretes a wide array of proteins, metabolites and non-coding RNAs (miRNAs) and that many of these secreted factors exert powerful effects on metabolic processes both in the liver and in peripheral tissues...

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 programmed endometrial mesenchymal progenitor/stem cells...

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 indicate that the elevated plasma concentrations of glucagon may also be associated with hepatic steatosis and not necessarily with the presence or absence of T2D...

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 fatty acids stimulate the release of serotonin from the duodenum promoting gut peristalsis and nutrient absorption...

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...

This review provides the reader with current insights on testicular adrenal rest tumors (TARTs), a complication in male patients with congenital adrenal hyperplasia (CAH).In recent studies, an overall TART prevalence of 40% (range 14-89%) in classic CAH-patients is found. Reported differences are mainly caused by the method of detection, and the selected patient population. Biochemically, histologically, and molecularly TARTs exhibit particular adrenal characteristics and were therefore thought to originate from aberrant adrenal cells...

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 provided remarkable improvements in survival...

The rediscovery of the group of thyronamines (TAMs), especially the first detailed description of their most prominent congener 3-iodothyronamine (3T1AM) 14 years ago, boosted research on this thyroid hormone metabolite tremendously. TAMs 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 TAMs as a therapeutic option. The G protein-coupled receptor (GPCR) TAAR1, a member of the trace amine-associated receptor (TAAR) family, was identified as the first target and effector of TAM action...

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 receptor mutations, combined deficiency of GH, prolactin, and TSH, or global deletion of GH receptors live longer than do 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 evolutionarily conserved trade-offs among aging, growth, maturation, fecundity, and the underlying anabolic processes...

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 affects 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 steroid milieu and possibly related to the metabolic costs of reproduction...

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 IGF-binding protein-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...