Review Articles in 2011

Estrogens regulate physiological and pathological processes in both women and men. Traditionally, the actions of 17β-estradiol, the predominant and most potent endogenous estrogen, were ascribed to two nuclear estrogen receptors (ERs), ERα and ERβ; however, transmembrane ERs, such as G-protein-coupled ER 1 (GPER), have been implicated in rapid estrogen signaling. This Review provides an overview of estrogen signaling and its receptors, with particular emphasis on GPER. It also highlights the importance of GPER in health and disease, such as cancer, for which GPER is a potential therapeutic target and prognostic indicator.

Gut microbes act as an environmental factor that affects an individual's physiology and metabolism, particularly in the context of obesity and its related metabolic disorders. This Review highlights how gut microbes alter the expression of genes involved in the development of obesity and inflammation and focuses on the potential role of specific nutrients that target the gut microbiota.

Many questions remain about the efficacy of radioiodine treatment for thyroid remnant ablation and therapy of advanced differentiated thyroid cancer. This Review intends to answer some of these questions taking into account novel insights into the treatment and (re)staging of patients with metastatic disease.

Epidemiological data show a worldwide increase in the prevalence and incidence of neuroendocrine neoplasms of the digestive tract and pancreas in the past few decades, which is probably due to improved methods of detection of these tumors. This Review provides a state-of-the-art discussion of the current diagnostic procedures and treatment options for these neuroendocrine neoplasms.

The anterior pituitary gland secretes hormones that regulate developmental and physiological processes, such as growth, the stress response, and reproduction. This Review summarizes the gene regulatory pathways that control anterior pituitary development, with emphasis on the role of the homeodomain transcription factors in normal pituitary organogenesis and heritable pituitary disease.

The cellular origin of thyroid cancer has not been fully elucidated. The author of this Review discusses the different mechanisms by which thyroid cancer stem cells might contribute to the development of thyroid cancer and the potential of stem-cell-based diagnostic and therapeutic strategies to improve the management of patients with thyroid cancer.

Osteoporosis is characterized by a decrease in bone mass and alterations in bone architecture that increase bone fragility and risk of fracture. Therapy with recombinant human PTH analogues increases BMD and bone mass and improves the microarchitecture of the skeleton. This Review summarizes the mechanism of action of PTH and discusses pharmacological data as well as the clinical uses of PTH analogues.

Many individuals with prediabetes have been shown to have neuropathy and vice versa. This Review summarizes the current evidence on the association between prediabetes and neuropathy and discusses the assessment of glucose metabolism as part of the diagnostic work-up for neuropathy.

Diabetes insipidus is a clinical syndrome characterized by the excretion of abnormally large volumes of dilute urine (polyuria) and increased fluid intake (polydipsia). This Review focuses on the clinical presentation, genetic basis and molecular mechanisms of the currently known familial forms of diabetes insipidus.

Diabetes mellitus is an established risk factor for periodontitis, and periodontitis can adversely affect glycemic control. This Review discusses the complex relationship between these two conditions and the implications of this association for patients and health-care professionals.

This Review provides a brief overview of the prevalence, clinical effect and management of endocrine incidentalomas with a focus on data regarding the diagnostic and therapeutic challenges imposed by incidentally discovered adrenal lesions.

Osteogenesis imperfecta, or 'brittle bone disease', is a clinically heterogeneous heritable connective tissue disorder, the causative defects of which are directly related to type I collagen. Human cases and murine models of osteogenesis imperfecta are providing insight into common pathways in dominant and recessive osteogenesis imperfecta, leading to the re-evaluation of its definition, classification and therapeutic approaches.

The authors of this Review integrate contributions of both central and peripheral glucagon-like peptide 1 (GLP-1), which is secreted from the intestine in response to nutrient ingestion, in a model of short-term and long-term control of energy balance. This model is discussed with respect to current GLP-1-based therapies and ongoing research that may help maximize the effectiveness of GLP-1-based treatment of obesity.

Sustained consumption of high amounts of nutrients replete with appetite-enhancing pro-oxidant advanced glycation endproducts (AGEs) is a crucial link between a positive energy balance and deleterious outcomes, such as insulin resistance and inflammation, and restriction of AGEs in nutrients improves both conditions. This Review focuses on AGEs as novel initiators of oxidative stress that precede rather than result from diabetes mellitus and illustrates the potential therapeutic gains from AGE restriction as an effective, cost-efficient strategy.

Primary aldosteronism is a common, but underdiagnosed, cause of curable arterial hypertension. This Review provides updated information to enable clinicians to identify patients with primary aldosteronism and for subtype differentiation to identify those with surgically curative forms of the disease.

A fully functional female reproductive tract is essential for the natural production of offspring; however, developmental abnormalities and disease can cause morbidity and mortality. This Review discusses the normal function of the reproductive tract and some of the major conditions that cause dysfunction, with a focus on endocrine-related dysfunction.

In this Review, Peggy Cohen-Kettenis and Baudewijntje Kreukels discuss the experience of the Amsterdam Gender Identity Clinic of using gonadotropin-releasing hormone analogs to suppress puberty in adolescents who have gender dysphoria. Although so far outcomes have been positive, more research is needed before their protocol can be widely recommended.

Thyrotoxic periodic paralysis (TPP) is an endocrine channelopathy that is often underdiagnosed. TPP results from the combination of genetic susceptibility, environmental factors and thyrotoxicosis. In this Review, the authors propose an integrated etiopathophysiological model of TPP that is based on molecular findings and knowledge gained from long-term follow-up of patients with TPP.

This Review examines the pathogenic interplay between insulin resistance and nonalcoholic fatty liver disease (NAFLD) as well as how NAFLD may predispose individuals to the development of type 2 diabetes mellitus. Furthermore, the effect of NAFLD upon vascular and liver-related morbidity and mortality in patients with type 2 diabetes mellitus is examined and potential treatment strategies are explored.

RNA interference (RNAi) is a robust gene silencing mechanism that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs. This Review describes the current status of research and clinical trials on RNAi-based therapeutics and addresses novel potential targets for the treatment of metabolic disease.