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Mechanisms maintaining the dormancy and survival of mammalian primordial follicles.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
To preserve the length of a woman's reproductive life it is essential that the majority of her ovarian primordial follicles are maintained in a quiescent state to provide a reserve for continuous reproductive success. The mechanisms maintaining the dormancy and survival of primordial follicles have been a mystery for decades. In recent years information provided by genetically modified mouse models has revealed a number of molecules whose functions are indispensable for the maintenance of follicular quiescence (including PTEN, Tsc1, Tsc2, Foxo3a, p27) and survival (PI3K signaling). Here we summarize this updated inform...
Source: Trends in Endocrinology and Metabolism: TEM - November 11, 2009 Category: Endocrinology Authors: Reddy P, Zheng W, Liu K Tags: Trends Endocrinol Metab Source Type: journals

The Dachshund gene in development and hormone-responsive tumorigenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The dachshund (dac) gene was initially described as a mutant phenotype in flies featuring extremely short legs relative to their body length. Functioning as a dominant suppressor of the ellipse mutation, a hypermorphic allele of the Epidermal Growth Factor Receptor (EGFR), the dac gene plays a key role in metazoan development, regulating ocular, limb, brain, and gonadal development. In the Drosophila eye, dac is a key component of the Retinal Determination Gene Network (RDGN) governing the normal initiation of the morphogenetic furrow and thereby eye development. Recent studies have demonstrated an important role for h...
Source: Trends in Endocrinology and Metabolism: TEM - November 5, 2009 Category: Endocrinology Authors: Popov VM, Wu K, Zhou J, Powell MJ, Mardon G, Wang C, Pestell RG Tags: Trends Endocrinol Metab Source Type: journals

WNT signaling in ovarian follicle biology and tumorigenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The WNTS are an expansive family of glycoprotein signaling molecules known mostly for the roles they play in embryonic development. WNT signaling first caught the attention of ovarian biologists when it was reported that the inactivation of Wnt4 in mice results in partial female-to-male sex reversal and oocyte depletion. More recently, studies using loss- and gain-of-function transgenic mouse models demonstrated the requirement for Wnt4, Fzd4 and Ctnnb1, components of the WNT pathway, for normal folliculogenesis, luteogenesis and steroidogenesis, and showed that dysregulated WNT signaling can cause granulosa cell tumor...
Source: Trends in Endocrinology and Metabolism: TEM - October 27, 2009 Category: Endocrinology Authors: Boyer A, Goff AK, Boerboom D Tags: Trends Endocrinol Metab Source Type: journals

Epigenetic mechanisms in the development of type 2 diabetes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Type 2 diabetes (T2D) is a disorder of complex genetics influenced by interactions between susceptible genetic loci and environmental perturbations. Intrauterine growth retardation is one such environmental perturbation linked to the development of T2D in adulthood. An abnormal metabolic intrauterine milieu affects fetal development by permanently modifying expression of key genes regulating beta-cell development (Pdx1) and glucose transport (Glut4) in muscle. Epigenetic regulation of gene expression is one mechanism by which genetic susceptibility and environmental insults can lead to T2D. Therefore, therapeutic agent...
Source: Trends in Endocrinology and Metabolism: TEM - October 26, 2009 Category: Endocrinology Authors: Pinney SE, Simmons RA Tags: Trends Endocrinol Metab Source Type: journals

Torpor induction in mammals: recent discoveries fueling new ideas.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
When faced with a harsh climate or inadequate food, some mammals enter a state of suspended animation known as torpor. A major goal of torpor research is to determine mechanisms that integrate environmental cues, gene expression and metabolism to produce periods of torpor lasting from hours to weeks. Recent discoveries spanning the Metazoa suggest that sirtuins, the mammalian circadian clock, fibroblast growth factor 21 (FGF21) and lipids are involved in torpor induction. For example, sirtuins link cellular energy status to the mammalian circadian clock, oxidative stress and metabolic fuel selection. In this review, we...
Source: Trends in Endocrinology and Metabolism: TEM - October 26, 2009 Category: Endocrinology Authors: Melvin RG, Andrews MT Tags: Trends Endocrinol Metab Source Type: journals

Chaperone-mediated autophagy: selectivity pays off.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Degradation of intracellular components in lysosomes, generically known as autophagy, can occur through different pathways. This review discusses chaperone-mediated autophagy (CMA), a type of autophagy set apart from other autophagic pathways owing to its selectivity and distinctive mechanism by which substrates reach the lysosomal lumen. CMA participates in quality control and provides energy to cells under persistently poor nutritional conditions. Alterations in CMA have recently been shown to underlie some severe human disorders for which the decline with age in the activity of this pathway might become a major aggr...
Source: Trends in Endocrinology and Metabolism: TEM - October 24, 2009 Category: Endocrinology Authors: Cuervo AM Tags: Trends Endocrinol Metab Source Type: journals

Leptin receptor modulation of adiposity and fertility.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The leptin receptor was discovered as a leptin binding protein, which is highly expressed in the choroid plexus. Mapping of the gene's chromosomal locations in rodents revealed that mutations in Lepr were the basis of obesity/diabetes mutations in rodents and humans. Genetic manipulations that target Lepr expression in specific neurons or hypothalamic areas have generated insights into the modes by which body composition and reproductive function are modulated by the leptin receptor. These animal models have also been instrumental in identifying diabetes susceptibility genes. In this review we discuss the evidence that...
Source: Trends in Endocrinology and Metabolism: TEM - October 23, 2009 Category: Endocrinology Authors: Israel D, Chua S Tags: Trends Endocrinol Metab Source Type: journals

The molecular basis of hypopituitarism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypopituitarism is defined as the deficiency of one or more of the hormones secreted by the pituitary gland. Several developmental factors necessary for pituitary embryogenesis and hormone secretion have been described, and mutations of these genes in humans provide a molecular understanding of hypopituitarism. Genetic studies of affected patients and their families provide insights into possible mechanisms of abnormal pituitary development; however, mutations are rare. This review characterizes several of these developmental proteins and their role in the pathogenesis of hypopituitarism. Continuing research is require...
Source: Trends in Endocrinology and Metabolism: TEM - October 22, 2009 Category: Endocrinology Authors: Romero CJ, Nesi-França S, Radovick S Tags: Trends Endocrinol Metab Source Type: journals

Hepatitis C virus hijacks host lipid metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hepatitis C virus (HCV) enhances its replication by modulating host cell lipid metabolism. HCV circulates in the blood in association with lipoproteins. HCV infection is associated with enhanced lipogenesis, reduced secretion, and beta-oxidation of lipids. HCV-induced imbalance in lipid homeostasis leads to steatosis. Many lipids are crucial for the virus life cycle, and inhibitors of cholesterol/fatty acid biosynthetic pathways inhibit virus replication, maturation and secretion. HCV negatively modulates the synthesis and secretion of very low-density lipoproteins (VLDL). Components involved in VLDL assembly are also ...
Source: Trends in Endocrinology and Metabolism: TEM - October 22, 2009 Category: Endocrinology Authors: Syed GH, Amako Y, Siddiqui A Tags: Trends Endocrinol Metab Source Type: journals

Does skeletal muscle oxidative stress initiate insulin resistance in genetically predisposed individuals?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Reactive oxygen species (ROS) are postulated to be a common trigger of insulin resistance. For example, treatment of adipocytes with either tumor-necrosis factor-alpha or dexamethasone increases ROS before impairing glucose uptake. Similarly, treatment with mitochondria-specific antioxidants preserves insulin sensitivity in animal models of insulin resistance. However, it remains unclear whether ROS contribute to insulin resistance in humans. First-degree relatives (FDRs) of type 2 diabetes subjects are at increased risk of developing insulin resistance and type 2 diabetes. Here we review the documented metabolic impai...
Source: Trends in Endocrinology and Metabolism: TEM - October 22, 2009 Category: Endocrinology Authors: Samocha-Bonet D, Heilbronn LK, Lichtenberg D, Campbell LV Tags: Trends Endocrinol Metab Source Type: journals

Challenging estrogen receptor beta with phosphorylation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
From classical gland-based endocrinology to nuclear hormone receptor biology, tremendous progress has been made in our understanding of hormone responses underlying cellular communication. Estrogen elicits a myriad of biological processes in reproductive and peripheral target tissues through its interaction with the estrogen receptors ERalpha and ERbeta. However, our knowledge of estrogen-dependent and independent action has mainly focused on ERalpha, leaving the role of ERbeta obscure. This review discusses our current understanding of ERbeta function and the emerging role of intracellular signals that act upon and ac...
Source: Trends in Endocrinology and Metabolism: TEM - October 15, 2009 Category: Endocrinology Authors: Sanchez M, Picard N, Sauvé K, Tremblay A Tags: Trends Endocrinol Metab Source Type: journals

Sex steroids and the male skeleton: a tale of two hormones.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Traditionally, the stronger male skeleton was considered to result from higher androgen levels in men compared to women. However, the regulation of male bone growth by sex steroids appears more complex than originally anticipated. Based on clinical observations and studies in animal models, not only androgens and androgen receptor (AR), but also estrogens and estrogen receptor-alpha (not ERbeta) are required for optimal bone mineral acquisition during male growth. In addition, both sex steroids are involved in the maintenance of male skeletal health. In fact, bone loss and fracture risk have been associated with estrog...
Source: Trends in Endocrinology and Metabolism: TEM - October 15, 2009 Category: Endocrinology Authors: Callewaert F, Boonen S, Vanderschueren D Tags: Trends Endocrinol Metab Source Type: journals

Lysophosphatidic acid (LPA) signaling in vertebrate reproduction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lysophosphatidic acid (LPA) is a cell membrane phospholipid metabolite that can act as an extracellular signal. Its effects are mediated through at least five G protein-coupled receptors, LPA(1-5), and probably others as well. Studies in multiple species including LPAR-deficient mice and humans have identified or implicated important roles for receptor-mediated LPA signaling in multiple aspects of vertebrate reproduction. These include ovarian function, spermatogenesis, fertilization, early embryo development, embryo implantation, embryo spacing, decidualization, pregnancy maintenance and parturition. LPA signaling can...
Source: Trends in Endocrinology and Metabolism: TEM - October 14, 2009 Category: Endocrinology Authors: Ye X, Chun J Tags: Trends Endocrinol Metab Source Type: journals

The EGFR network in bone biology and pathology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The resorption, formation and maintenance of bone are coordinated by the action of several hormones, growth factors and transcription factors. Recent experiments based on genetically modified mouse models, gene microarrays and pharmacological intervention indicate that the epidermal growth factor receptor (EGFR) system plays important roles in skeletal biology and pathology. This network, including a family of seven growth factors - the EGFR ligands - and the related tyrosine kinase receptors EGFR (ERBB1), ERBB2, ERBB3 and ERBB4, regulates aspects such as proliferation and differentiation of osteoblasts, chondrocytes a...
Source: Trends in Endocrinology and Metabolism: TEM - October 8, 2009 Category: Endocrinology Authors: Schneider MR, Sibilia M, Erben RG Tags: Trends Endocrinol Metab Source Type: journals

Energetic cell sensors: a key to metabolic homeostasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent breakthrough studies suggest that metabolic signals such as AMP/NAD(+) and acetyl-CoA during fasting and feeding, respectively, translate the energetic cell status into specific transcriptional metabolic programs. Notably, NAD(+) and acetyl-CoA modulate chromatin packaging and gene expression as substrates of histone deacetylases or histone acetyltransferases, respectively. These energetic sensors regulate circadian rhythms and their related physiological processes. In addition, NAD(+) indirectly activates peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) during fasting, whereas ac...
Source: Trends in Endocrinology and Metabolism: TEM - October 8, 2009 Category: Endocrinology Authors: Naïmi M, Arous C, Van Obberghen E Tags: Trends Endocrinol Metab Source Type: journals

The hinge region: an important receptor component for GPHR function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glycoprotein hormone receptors (GPHRs) are members of the seven-transmembrane-spanning receptor family characterized by a large ectodomain. The hinge region belongs to a part of the GPHR ectodomain for which the three-dimensional structure has not yet been deciphered, leaving important questions unanswered concerning ligand binding and GPHR activation. Recent publications indicate that specific residues of the hinge region mediate hormone binding, receptor activation and/or intramolecular signaling for the three GPHRs, emphasizing the importance of this region. Based on these findings, the hinge region is involved at l...
Source: Trends in Endocrinology and Metabolism: TEM - October 8, 2009 Category: Endocrinology Authors: Mueller S, Jaeschke H, Günther R, Paschke R Tags: Trends Endocrinol Metab Source Type: journals

Insulin, leptin and reward.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Feeding for pleasure, or "non-homeostatic feeding", potentially contributes to the rapid development of obesity worldwide. Obesity is associated with an imbalance of regulatory hormones which normally act to maintain stable energy balance and body weight. The adiposity hormones insulin and leptin are two such signals elevated in obesity with the capacity to dampen feeding behavior through their action on hypothalamic circuits which regulate appetite and metabolism. Recent evidence suggests that both hormones achieve this degree of regulation by inhibiting the rewarding aspects of feeding behavior, perhaps by signaling ...
Source: Trends in Endocrinology and Metabolism: TEM - October 6, 2009 Category: Endocrinology Authors: Davis JF, Choi DL, Benoit SC Tags: Trends Endocrinol Metab Source Type: journals

Glucose transporters in gametes and preimplantation embryos.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The oocyte, sperm and preimplantation embryo have unique metabolic needs that must be met to ensure successful pregnancy. The family of facilitative glucose transporters (GLUTs) plays a major role in providing metabolic substrates to these tissues. The variety of GLUTs expressed in these tissues allows for flexibility to adapt to a changing environment. Alterations in glucose transport and metabolism at the earliest stages of development can impact fetal development. Research into the mechanisms of normal glucose transport into cells is critical for improving outcomes in the increasingly common diabetic maternal enviro...
Source: Trends in Endocrinology and Metabolism: TEM - October 4, 2009 Category: Endocrinology Authors: Purcell SH, Moley KH Tags: Trends Endocrinol Metab Source Type: journals

Actions of IGF binding proteins and related proteins in adipose tissue.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The insulin-like growth factors (IGFs), their binding proteins (IGFBPs) and structurally related proteins have been identified in adipose tissue but their roles in adipose tissue are poorly understood. IGF-I and IGFBP-3 expression increase during human preadipocyte differentiation. However, whereas IGF-I stimulates this process, IGFBP-3 is inhibitory both to preadipocyte differentiation and to differentiated adipocyte function. The direct interaction of IGFBP-3 with peroxisome proliferator-activated receptor-gamma is believed to contribute to its inhibitory effect on differentiation. Connective tissue growth factor (CT...
Source: Trends in Endocrinology and Metabolism: TEM - October 1, 2009 Category: Endocrinology Authors: Baxter RC, Twigg SM Tags: Trends Endocrinol Metab Source Type: journals

Purinergic regulation of hypothalamopituitary functions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The hypothalamus controls the release of hormones by the pituitary and is involved in control of food and water intake, sexual behavior, reproduction and daily cycles in physiological state and behavior, temperature regulation and emotional responses. Adenosine-5'-triphosphate (ATP) and its metabolic products contribute to these functions, acting as agonists for adenosine and P2Y receptors and two-transmembrane domain P2X receptor channels. This review summarizes the recent findings on purinergic receptor expression and their roles in signaling and cellular function in secretory and supporting cells of the hypothalamop...
Source: Trends in Endocrinology and Metabolism: TEM - September 30, 2009 Category: Endocrinology Authors: Stojilkovic SS Tags: Trends Endocrinol Metab Source Type: journals

Acute insulin resistance following injury.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hyperglycemia and insulin resistance often occur following injury and/or critical illness. Whereas intensive insulin treatment reduces hyperglycemia, mortality and morbidity in certain patients, little is known regarding the pathophysiology of acute insulin resistance following injury and infection. Studies suggest that acute insulin resistance is complex and might differ in a tissue-specific manner, involving multiple causative factors and intracellular signaling pathways. Therefore, the advantages of intensive insulin therapy might not be uniform to all injuries or critical illnesses. Clearly, the increased incidence...
Source: Trends in Endocrinology and Metabolism: TEM - September 30, 2009 Category: Endocrinology Authors: Li L, Messina JL Tags: Trends Endocrinol Metab Source Type: journals

ATF4-dependent transcription mediates signaling of amino acid limitation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mammals respond to dietary nutrient fluctuations; for example, deficiency of dietary protein or an imbalance of essential amino acids activates an amino acid response (AAR) signal transduction pathway, consisting of detection of uncharged tRNA by the GCN2 kinase, eIF2alpha phosphorylation and ATF4 expression. In concert with heterodimerization partners, ATF4 activates specific genes via a (CCAAT-enhancer binding protein-activating transcription factor response element (CARE). This review outlines the ATF4-dependent transcriptional mechanisms associated with the AAR, focusing on progress during the past 5 years. Recent ...
Source: Trends in Endocrinology and Metabolism: TEM - September 29, 2009 Category: Endocrinology Authors: Kilberg MS, Shan J, Su N Tags: Trends Endocrinol Metab Source Type: journals

Genome-wide mechanisms of nuclear receptor action.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nuclear receptors are involved in a myriad of physiological processes, responding to ligands and binding to DNA at sequence-specific cis-regulatory elements. This binding occurs in the context of chromatin, a critical factor in regulating eukaryotic transcription. Recent high-throughput assays have examined nuclear receptor action genome-wide, advancing our understanding of receptor binding to regulatory elements. Here, we discuss current knowledge of genome-wide response element occupancy by receptors and the function of transcription factor networks in regulating nuclear receptor action. We highlight emerging roles f...
Source: Trends in Endocrinology and Metabolism: TEM - September 29, 2009 Category: Endocrinology Authors: Biddie SC, John S, Hager GL Tags: Trends Endocrinol Metab Source Type: journals

Meta-regulation: microRNA regulation of glucose and lipid metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Maintenance of homeostasis during environmental flux requires constant metabolic adjustment, achieved partly through the fine regulation of gene expression. MicroRNAs are key players in this regulatory milieu; they have been implicated in regulating gene expression within several metabolically active tissues including the endocrine pancreas, liver and adipose tissue. Recent studies, for example, implicate miR-375 in pancreatic islet cell viability and function, and removal or overexpression of miR-375 profoundly affects glucose metabolism. In the liver, miR-122 is important for normal lipid metabolism. In fact, misexpr...
Source: Trends in Endocrinology and Metabolism: TEM - September 29, 2009 Category: Endocrinology Authors: Lynn FC Tags: Trends Endocrinol Metab Source Type: journals

Mineralocorticoid receptors in the metabolic syndrome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The mineralocorticoid receptor (MR) mediates aldosterone effects on salt homeostasis and blood pressure regulation. MR activation also promotes inflammation, cardiovascular remodelling and endothelial dysfunction, and affects adipose tissue differentiation and function. Some of these effects derive from MR activation by glucocorticoids. Recent epidemiological studies show that the incidence of metabolic syndrome increases across quartiles of aldosterone, implicating the MR as a central player in metabolic homeostasis, involving electrolyte, water and energy balance. This review summarizes the current understanding of M...
Source: Trends in Endocrinology and Metabolism: TEM - September 29, 2009 Category: Endocrinology Authors: Zennaro MC, Caprio M, Fève B Tags: Trends Endocrinol Metab Source Type: journals

The skinny on fat: lipolysis and fatty acid utilization in adipocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lipolysis for the provision of fatty acids (FA) for other organs during times of energy demand occurs uniquely in white adipose tissue (WAT). Recent findings have identified a bona fide TAG hydrolase and the major adipose phospholipase A(2), AdPLA. By controlling PGE(2) levels, AdPLA dominantly regulates lipolysis in an autocrine/paracrine manner. Moreover, recent findings demonstrate that, surprisingly, increasing lipolysis in adipose tissue does not necessarily increase serum FA levels, which are usually correlated with insulin resistance. Rather, increasing lipolysis in adipose tissue causes a shift within adipocyte...
Source: Trends in Endocrinology and Metabolism: TEM - September 28, 2009 Category: Endocrinology Authors: Ahmadian M, Duncan RE, Sul HS Tags: Trends Endocrinol Metab Source Type: journals

Adipose tissue expandability and the early origins of PCOS.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The most prevalent phenotypes of polycystic ovary syndrome (PCOS) are characterized by insulin resistance and androgen excess. The adipose tissue (AT) expandability hypothesis explains the development of insulin resistance in obesity and in cases of AT deficit. In line with this hypothesis, we propose that hyperinsulinemic androgen excess in PCOS is often underpinned by exhaustion of the capacity to expand subcutaneous AT in a metabolically safe way. Such exhaustion might occur when a positive energy imbalance meets a normal fat-storage capacity and/or when a normal energy balance faces a low fat storage capacity. This...
Source: Trends in Endocrinology and Metabolism: TEM - September 28, 2009 Category: Endocrinology Authors: de Zegher F, Lopez-Bermejo A, Ibáñez L Tags: Trends Endocrinol Metab Source Type: journals

RAGE, glomerulosclerosis and proteinuria: Roles in podocytes and endothelial cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The multi-ligand Receptor for Advanced Glycation Endproducts (RAGE) is expressed in podocytes and endothelial cells in the human and murine glomerulus. Although present at low levels in homeostasis, RAGE expression is increased during disease. Pharmacological antagonism of RAGE or its genetic deletion imparts marked protection from podocyte effacement, albuminuria and glomerular sclerosis in disease models. In human subjects, associations between specific genetic polymorphisms of RAGE and levels of soluble forms of RAGE are linked to disease states in the kidney. In this review, we summarize the evidence from mouse to ...
Source: Trends in Endocrinology and Metabolism: TEM - September 24, 2009 Category: Endocrinology Authors: D'Agati V, Yan SF, Ramasamy R, Schmidt AM Tags: Trends Endocrinol Metab Source Type: journals

Systems biology asks new questions about sex differences.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Females and males differ in physiology and in the incidence and progression of diseases. The sex-biased proximate factors causing sex differences in phenotype include direct effects of gonadal hormones and of genes represented unequally in the genome because of their X- or Y-linkage. Novel systems approaches have begun to assess the magnitude and character of sex differences in organization of gene networks on a genome-wide scale. These studies identify functionally related modules of genes that are coexpressed differently in males and females, and sites in the genome that regulate gene networks in a sex-specific manne...
Source: Trends in Endocrinology and Metabolism: TEM - September 21, 2009 Category: Endocrinology Authors: Arnold AP, van Nas A, Lusis AJ Tags: Trends Endocrinol Metab Source Type: journals

Plasma Membrane Estrogen Receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is now firmly established that estrogen and all sex steroid receptors exist in discrete cellular pools outside the nucleus. Estrogen receptors (ER) have been localized to the plasma membrane where both ERalpha and ERbeta function in a wide variety of cells and organs. ERs have also been found in discrete cytoplasmic organelles including mitochondria and the endoplasmic reticulum. In ligand-dependent fashion, each ER pool contributes to the overall, integrated effects of estrogens producing biological outcomes. This review highlights the recent work establishing new roles and targets of membrane ER signaling. Such ac...
Source: Trends in Endocrinology and Metabolism: TEM - September 21, 2009 Category: Endocrinology Authors: Levin ER Tags: Trends Endocrinol Metab Source Type: journals

beta-Cell deterioration during diabetes: what's in the gun?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Clinical management of patients with type 2 diabetes (T2D) successfully prevents extreme hyperglycemia but does not precisely control glucose levels throughout the day. The pathogenesis of T2D is akin to a double-barrel shotgun. The first trigger causes an explosion that sets genetic expression of the disease in motion; the second trigger discharges a host of environmental factors that worsen its clinical course. Candidate shells include glucolipotoxicity, cytokines, oxidative and endoplasmic reticulum stress and insulin resistance. This review considers how each candidate adversely impacts beta-cell function to create...
Source: Trends in Endocrinology and Metabolism: TEM - September 10, 2009 Category: Endocrinology Authors: Robertson RP Tags: Trends Endocrinol Metab Source Type: journals

Functional implications of genetic variation in human PPARgamma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The peroxisome proliferator-activated receptor gamma (PPARgamma) plays a key role in the regulation of lipid and glucose metabolism. Human genetic evidence supporting this view comes from the study of both common (e.g. the Pro12Ala polymorphism) and rare (loss-of-function mutations) variants in the gene encoding PPARgamma. Indeed, patients harbouring mutant PPARgamma exhibit familial partial lipodystrophy type 3 and an extreme monogenic form of the metabolic syndrome. The recent elucidation of the crystal structure of the full-length PPARgamma-RXRalpha heterodimer bound to DNA has shed new light on the functional conse...
Source: Trends in Endocrinology and Metabolism: TEM - September 9, 2009 Category: Endocrinology Authors: Jeninga EH, Gurnell M, Kalkhoven E Tags: Trends Endocrinol Metab Source Type: journals

Depression as a risk factor for osteoporosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Osteoporosis is a major public health threat. Multiple studies have reported an association between depression and low bone mineral density, but a causal link between these two conditions is disputed. Here we review the endocrine and immune alterations secondary to depression that might affect bone mass. We also discuss the possible role of poor lifestyle in the etiology of osteoporosis in subjects with depression and the potential effect of antidepressants on bone loss. We propose that depression induces bone loss and osteoporotic fractures, primarily via specific immune and endocrine mechanisms, while poor lifestyle ...
Source: Trends in Endocrinology and Metabolism: TEM - September 8, 2009 Category: Endocrinology Authors: Cizza G, Primma S, Csako G Tags: Trends Endocrinol Metab Source Type: journals

The hypothalamic GnRH pulse generator: multiple regulatory mechanisms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pulsatile secretion of gonadotropin-releasing hormone (GnRH) release is an intrinsic property of hypothalamic GnRH neurons. Pulse generation has been attributed to multiple specific mechanisms, including spontaneous electrical activity of GnRH neurons, calcium and cAMP signaling, a GnRH receptor autocrine regulatory component, a GnRH concentration-dependent switch in GnRH receptor (GnRH-R) coupling to specific G proteins, the expression of G protein-coupled receptors (GPCRs) and steroid receptors, and homologous and heterologous interactions between cell membrane receptors expressed in GnRH neurons. The coexistence of ...
Source: Trends in Endocrinology and Metabolism: TEM - September 6, 2009 Category: Endocrinology Authors: Krsmanovic LZ, Hu L, Leung PK, Feng H, Catt KJ Tags: Trends Endocrinol Metab Source Type: journals

Potential vascular actions of 2-methoxyestradiol.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
2-Methoxyestradiol (2-ME) is a biologically active metabolite of 17beta-estradiol that appears to inhibit key processes associated with cell replication in vitro. The molecule has been suggested to have potent growth-inhibitory effects on proliferating cells, including smooth muscle cells and endothelial cells, and may be antiangiogenic. Because of these potential roles for 2-ME, its lack of cytotoxicity and low estrogenic activity, we hypothesize that 2-ME could be a valuable therapeutic molecule for prevention and treatment of cardiovascular diseases. Whether 2-ME is as effective in vivo as it is in vitro at modulati...
Source: Trends in Endocrinology and Metabolism: TEM - September 3, 2009 Category: Endocrinology Authors: Dubey RK, Jackson EK Tags: Trends Endocrinol Metab Source Type: journals

GPR30/GPER1: searching for a role in estrogen physiology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Estrogens are sex hormones that are central to health and disease in both genders. These hormones have long been recognized to act in complex ways, both through relatively slow genomic mechanisms and via fast non-genomic mechanisms. Several recent in vitro studies suggest that GPR30, or G protein-coupled estrogen receptor 1 (GPER1), is a functional membrane estrogen receptor involved in non-genomic estrogen signaling. However, this function is not universally accepted. Studies concerning the role of GPER1 in vivo are now beginning to appear but with divergent results. In this review we discuss current knowledge on the ...
Source: Trends in Endocrinology and Metabolism: TEM - September 3, 2009 Category: Endocrinology Authors: Olde B, Leeb-Lundberg LM Tags: Trends Endocrinol Metab Source Type: journals

Mitochondrial generation of free radicals and hypoxic signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Most reactive oxygen species (ROS) are generated in cells by the mitochondrial respiratory chain. Mitochondrial ROS production is modulated largely by the rate of electron flow through respiratory chain complexes. Recently, it has become clear that under hypoxic conditions, the mitochondrial respiratory chain also produces nitric oxide (NO), which can generate other reactive nitrogen species (RNS). Although excess ROS and RNS can lead to oxidative and nitrosative stress, moderate to low levels of both function in cellular signaling pathways. Especially important are the roles of these mitochondrially generated free rad...
Source: Trends in Endocrinology and Metabolism: TEM - September 2, 2009 Category: Endocrinology Authors: Poyton RO, Ball KA, Castello PR Tags: Trends Endocrinol Metab Source Type: journals

Prohibitin and mitochondrial biology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prohibitins are ubiquitous, evolutionarily conserved proteins that are mainly localized in mitochondria. The mitochondrial prohibitin complex comprises two subunits, PHB1 and PHB2. These two proteins assemble into a ring-like macromolecular structure at the inner mitochondrial membrane and are implicated in diverse cellular processes: from mitochondrial biogenesis and function to cell death and replicative senescence. In humans, prohibitins have been associated with various types of cancer. While their biochemical function remains poorly understood, studies in organisms ranging from yeast to mammals have provided signi...
Source: Trends in Endocrinology and Metabolism: TEM - September 2, 2009 Category: Endocrinology Authors: Artal-Sanz M, Tavernarakis N Tags: Trends Endocrinol Metab Source Type: journals

Role of IGF-I in skeletal muscle mass maintenance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The recent identification of signaling elements that regulate skeletal muscle protein balance has provided the opportunity to determine how IGF-I alters these processes. Animal studies have revealed the important role of IGF-I in preventing muscle atrophy and enabled investigators to determine the hierarchy of signaling pathways and events within each pathway that are modulated by IGF-I. These discoveries provide opportunity for future studies to target these important signaling events and develop strategies to reverse loss of muscle mass that accompanies these catabolic states. Because there are no approved medical th...
Source: Trends in Endocrinology and Metabolism: TEM - August 31, 2009 Category: Endocrinology Authors: Clemmons DR Tags: Trends Endocrinol Metab Source Type: journals

FGFs in endochondral skeletal development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The mammalian skeleton forms and grows through two developmental pathways: membranous ossification, which gives rise to calvarial bones and the distal clavicle, and endochondral ossification, which is responsible for the bones of the limbs, girdles, vertebrae, face, base of the skull and the medial clavicle. The regulation of both pathways is extremely complex, and the rules that govern it are still emerging. However, it has become clear that fibroblast growth factors (FGFs) and their cognate receptors (FGFRs) play essential roles. This review focuses on the roles of FGFs and FGFRs in endochondral skeletal development,...
Source: Trends in Endocrinology and Metabolism: TEM - August 26, 2009 Category: Endocrinology Authors: Horton WA, Degnin CR Tags: Trends Endocrinol Metab Source Type: journals

Thyroid receptor: roles in cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The thyroid hormone receptors, encoded by the TRalpha and TRbeta genes, are ligand-dependent transcription factors that belong to the nuclear receptor superfamily. In addition to the role of these receptors in growth, development and metabolism, there is increasing evidence that they also inhibit transformation and act as tumor suppressors. Aberrant TR action, as well as receptor silencing, are common events in human cancer, and TRs also have an important role in tumor progression in experimental animal models, suggesting that these receptors constitute a novel therapeutic target in cancer. This review highlights recen...
Source: Trends in Endocrinology and Metabolism: TEM - August 25, 2009 Category: Endocrinology Authors: Aranda A, Martínez-Iglesias O, Ruiz-Llorente L, García-Carpizo V, Zambrano A Tags: Trends Endocrinol Metab Source Type: journals

Caloric restriction, SIRT1 and longevity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
More than 70 years after its initial report, caloric restriction stands strong as the most consistent non-pharmacological intervention increasing lifespan and protecting against metabolic disease. Among the different mechanisms by which caloric restriction might act, Sir2/SIRT1 (Silent information regulator 2/Silent information regulator T1) has been the focus of much attention because of its ability to integrate sensing of the metabolic status with adaptive transcriptional outputs. This review focuses on gathered evidence suggesting that Sir2/SIRT1 is a key mediator of the beneficial effects of caloric restriction and...
Source: Trends in Endocrinology and Metabolism: TEM - August 24, 2009 Category: Endocrinology Authors: Cantó C, Auwerx J Tags: Trends Endocrinol Metab Source Type: journals

Endocrine disruptors in female reproductive tract development and carcinogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Growing concerns over endocrine disrupting chemicals (EDCs) and their effects on human fetal development and adult health have promoted research into the underlying molecular mechanisms of endocrine disruption. Gene targeting technology has allowed insight into the genetic pathways governing reproductive tract development and how exposure to EDCs during a critical developmental window can alter reproductive tract development, potentially forming the basis for adult diseases. This review primarily uses diethylstilbestrol (DES) as a model agent for EDCs and discusses the recent progress elucidating how DES and other EDCs...
Source: Trends in Endocrinology and Metabolism: TEM - August 23, 2009 Category: Endocrinology Authors: Ma L Tags: Trends Endocrinol Metab Source Type: journals

Methylglyoxal: possible link between hyperglycaemia and immune suppression?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
No matter the cause of diabetes, the result is always hyperglycaemia. This excess glucose metabolism drives several damage pathways and raises concentrations of the reactive dicarbonyl, methylglyoxal (MG). MG can modify the structure and function of target molecules by forming advanced glycation end-products (AGEs) that act through their receptor (RAGE) to perpetuate vascular and neuronal injury responsible for long-term complications of diabetes. Diabetes patients also suffer lower resistance to many common infections, although the cause(s) for this lower resistance remains elusive. Here, we review recent evidence con...
Source: Trends in Endocrinology and Metabolism: TEM - August 23, 2009 Category: Endocrinology Authors: Price CL, Knight SC Tags: Trends Endocrinol Metab Source Type: journals

eNOS, metabolic syndrome and cardiovascular disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Large epidemiologic studies have established that diabetes, hyperlipidemia and obesity all increase the risk for cardiovascular disease. However, the precise mechanisms by which these metabolic disorders increase the propensity to develop atherosclerosis are not known. Recently, the concept of the metabolic syndrome - a constellation of conditions including obesity, hypertension, hyperlipidemia and insulin resistance - has received much attention. Studies on the metabolic syndrome might enable a better understanding of the underlying biological mechanisms that lead to cardiovascular disease. This review focuses on endo...
Source: Trends in Endocrinology and Metabolism: TEM - July 29, 2009 Category: Endocrinology Authors: Huang PL Tags: Trends Endocrinol Metab Source Type: journals

The changing shape of mitochondrial apoptosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondria are key organelles in conversion of energy, regulation of cellular signaling and amplification of programmed cell death. The anatomy of the organelle matches this functional versatility in complexity and is modulated by the concerted action of proteins that impinge on its fusion-fission equilibrium. A growing body of evidence implicates changes in mitochondrial shape in the progression of apoptosis and, therefore, proteins governing such changes are likely candidates for involvement in pathogenetic mechanisms in neurodegeneration and cancer. Here, we discuss the recent advancements in our knowledge about t...
Source: Trends in Endocrinology and Metabolism: TEM - July 29, 2009 Category: Endocrinology Authors: Wasilewski M, Scorrano L Tags: Trends Endocrinol Metab Source Type: journals

Role of Dicer in female fertility.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dicer is an RNAse III endonuclease that is essential for the biogenesis of microRNAs and small interfering RNAs. These small RNAs post-transcriptionally regulate mRNA gene expression through several mechanisms to affect key cellular events including proliferation, differentiation and apoptosis. Recently, the role of Dicer function in female reproductive tissues has begun to be elucidated through the use of knockout mouse models. Loss of Dicer within ovarian granulosa cells, luteal tissue, oocyte, oviduct and, potentially, the uterus renders females infertile. This review discusses these early studies and other data des...
Source: Trends in Endocrinology and Metabolism: TEM - July 28, 2009 Category: Endocrinology Authors: Luense LJ, Carletti MZ, Christenson LK Tags: Trends Endocrinol Metab Source Type: journals

Signals of youth: endocrine regulation of aging in Caenorhabditis elegans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Aging research has advanced greatly in the nematode Caenorhabditis elegans over the past 20 years, and we are now beginning to piece together distinct pathways that impinge on the aging process. The knowledge base that has been obtained through genetic analysis strongly suggests that endocrine signalling has a key role in most, if not all, of the pathways that alter the aging process of multicellular organisms such as the worm. In this review, we provide an overview of two well-studied aging pathways in C. elegans, the insulin/IGF-1 and germline signalling pathways, in which endocrine signalling is clearly important. W...
Source: Trends in Endocrinology and Metabolism: TEM - July 28, 2009 Category: Endocrinology Authors: Panowski SH, Dillin A Tags: Trends Endocrinol Metab Source Type: journals

What is the true nature of the osteoblastic hematopoietic stem cell niche?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The recently revitalized interest in the regulation of hematopoietic stem cells (HSCs) by the bone marrow microenvironment has resulted in the identification of some important cell types that potentially form the HSC niche. The term 'osteoblast' has commonly been used to describe the endosteal elements of the HSC niche, but these cells are part of a larger family that functions in bone at different stages of differentiation. Given that there is much controversy as to what cell types have important roles in the HSC niche, this review offers an overview of the diverse osteoblastic cell types and discusses the current evi...
Source: Trends in Endocrinology and Metabolism: TEM - July 9, 2009 Category: Endocrinology Authors: Askmyr M, Sims NA, Martin TJ, Purton LE Tags: Trends Endocrinol Metab Source Type: journals

PXR and CAR in energy metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The nuclear receptors pregnane X receptor (PXR, or NR1I2) and constitutive androstane receptor (CAR, or NR1I3) were originally identified as xenosensors that regulate the expression of Phase I and Phase II drug-metabolizing enzymes and transporters. Recent results suggest that PXR and CAR also have important endobiotic roles in energy metabolism by affecting the metabolism of fatty acids, lipids and glucose. PXR and CAR exert their effects on energy metabolism through direct gene regulation or through crosstalk with other transcriptional regulators. This review focuses on the roles of CAR and PXR in energy metabolism a...
Source: Trends in Endocrinology and Metabolism: TEM - July 9, 2009 Category: Endocrinology Authors: Wada T, Gao J, Xie W Tags: Trends Endocrinol Metab Source Type: journals