Des-acyl ghrelin: a metabolically active Peptide.
Abstract
Unacylated ghrelin (UAG), or des-acyl ghrelin, is slowly fighting its way up into the field of interest that studies preproghrelin gene-encoded peptides. Long considered to be an inert degradation product of (acylated) ghrelin (AG), UAG nowadays emerges as an important hormone, separate from the other proghrelin-derived peptides, AG and obestatin. UAG appears to have its own receptor, and it can share this receptor with AG, under experimental conditions at least. An increasing number of studies suggest that UAG can act as a potent functional inhibitor of ghrelin. It can even strongly suppress ghre...
Source: Endocrine Development - May 25, 2013 Category: Endocrinology Authors: Delhanty PJ, Neggers SJ, van der Lely AJ Tags: Endocr Dev Source Type: research
Ghrelin and tumors.
Abstract
Since the original discovery of ghrelin and, subsequently, obestatin (the alternative product of the ghrelin gene), a major interest has been devoted to the investigation of their central and peripheral activities in physiological conditions as well as on their role in metabolic diseases. However, several studies with different methodological approaches variably identified ghrelin and obestatin synthesis and secretion in several neoplastic conditions, including neuroendocrine and non-neuroendocrine cancers of various sites. Moreover, in vitro studies showed the capability of ghrelin to modulate tu...
Source: Endocrine Development - May 25, 2013 Category: Endocrinology Authors: Papotti M, Duregon E, Volante M Tags: Endocr Dev Source Type: research
Ghrelin function in insulin release and glucose metabolism.
Abstract
Given its wide spectrum of biological activities such as growth hormone (GH) release, feeding stimulation, adiposity and cardiovascular actions, the discovery of ghrelin opened many new perspectives within neuroendocrine, metabolic and cardiovascular research, thus suggesting its possible clinical application. Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues. Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue...
Source: Endocrine Development - May 25, 2013 Category: Endocrinology Authors: Dezaki K Tags: Endocr Dev Source Type: research
Products of the Ghrelin Gene, the Pancreatic β-Cell and the Adipocyte.
Abstract
The ghrelin system comprises acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin, besides the receptor for AG, the growth hormone (GH) secretagogue receptor type 1a (GHS-R1a), and the enzyme-promoting ghrelin acylation, ghrelin O-acyltransferase (GOAT). The ghrelin peptides exert a variety of biological actions, including regulation of energy homeostasis and glucose metabolism, as well as survival and proliferative effects in different cell types. Besides the stomach, its main site of production, ghrelin is expressed in pancreatic islets, where it represents an independent islet cell pop...
Source: Endocrine Development - May 25, 2013 Category: Endocrinology Authors: Granata R, Ghigo E Tags: Endocr Dev Source Type: research
Clinical perspectives for ghrelin-derived therapeutic products.
Abstract
Because of its orexigenic, adipogenic and diabetogenic activities, acylated ghrelin (AG) has emerged as an attractive target for the treatment of obesity and type 2 diabetes. Pharmacological tools have been designed in order to antagonize or block the hormone's activity, or inhibit ghrelin O-acyltransferase (GOAT), the enzyme that catalyzes its acylation. AG antagonists, shown to be potent inhibitors of growth hormone (GH) secretion, were not able to consistently induce the desirable metabolic effects. Some of them, on the contrary, acted as AG agonists. Similarly, AG-blocking agents including Spi...
Source: Endocrine Development - May 25, 2013 Category: Endocrinology Authors: Allas S, Abribat T Tags: Endocr Dev Source Type: research
Author index.
Authors:
PMID: 23652402 [PubMed - in process] (Source: Endocrine Development)
Source: Endocrine Development - May 25, 2013 Category: Endocrinology Tags: Endocr Dev Source Type: research
Subject index.
Authors:
PMID: 23652403 [PubMed - in process] (Source: Endocrine Development)
Source: Endocrine Development - May 25, 2013 Category: Endocrinology Tags: Endocr Dev Source Type: research
Title page / table of contents / preface.
Authors:
PMID: 23652404 [PubMed - in process] (Source: Endocrine Development)
Source: Endocrine Development - May 25, 2013 Category: Endocrinology Tags: Endocr Dev Source Type: research
Thyroid hormone transporters and resistance.
Abstract
Cellular entry is an important step preceding intracellular metabolism and action of thyroid hormone (TH). Transport of TH across the plasma membrane does not take place by simple diffusion but requires transporter proteins. One of the most effective and specific TH transporters identified to date is monocarboxylate transporter 8 (MCT8), the gene of which is located on the X chromosome. Although MCT8 is expressed in many tissues, its function appears to be most critical in the brain. Hemizygous MCT8 mutations in males cause severe psychomotor retardation, known as the Allan-Herndon-Dudley syndrome...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Visser TJ Tags: Endocr Dev Source Type: research
Genetics and epigenetics of parathyroid hormone resistance.
Abstract
End-organ resistance to the actions of parathyroid hormone (PTH) is defined as pseudohypoparathyroidism (PHP). Described originally by Fuller Albright and his colleagues in early 1940s, this rare genetic disease is subclassified into two types according to the nephrogenous response to the administration of biologically active PTH. In type I, the PTH-induced urinary excretion of both phosphate and cyclic AMP (cAMP) is blunted. In type II, only the PTH-induced urinary excretion of phosphate is blunted, while the cAMP response is unimpaired. Different subtypes of PHP type I have been described based ...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Bastepe M Tags: Endocr Dev Source Type: research
Gonadotropin resistance.
Abstract
Pituitary gonadotropins are essential for normal reproductive function. LH and FSH exert their effects by acting on G protein-coupled receptors. Pituitary LH and placental hCG share the same receptor (LHCGR). Homozygous or compound heterozygous inactivating mutations of LHCGR are associated with a phenotypic spectrum from female or ambiguous external genitalia due to Leydig cell hypoplasia to micropenis, hypergonadotropic hypogonadism and delayed puberty in genetic males. Testes size is slightly reduced, and testosterone levels are low in affected males. Interestingly, the clinical phenotypes are ...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Latronico AC, Arnhold IJ Tags: Endocr Dev Source Type: research
Clinical and molecular aspects of androgen insensitivity.
Abstract
Androgen insensitivity describes the inability of cells to respond adequately to androgens. The clinical aspects are well characterized and described in the androgen insensitivity syndrome, where underandrogenization occurs despite normal to high levels of androgens. In 46,XY individuals, this is associated with a variable phenotype ranging from completely female to ambiguous genitalia and infertility in males with gynecomastia. Androgen action is facilitated by a single androgen receptor (AR), whose gene is localized on the X chromosome. However, the identification of mutations in the AR gene in ...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Hiort O Tags: Endocr Dev Source Type: research
Exploring the molecular mechanisms of glucocorticoid receptor action from sensitivity to resistance.
Abstract
Glucocorticoids regulate a variety of physiological processes, and are commonly used to treat disorders of inflammation, autoimmune diseases, and cancer. Glucocorticoid action is predominantly mediated through the classic glucocorticoid receptor (GR), but sensitivity to glucocorticoids varies among individuals, and even within different tissues from the same individual. The molecular basis of this phenomenon can be partially explained through understanding the process of generating bioavailable ligand and the molecular heterogeneity of the GR. The molecular mechanisms that regulate glucocorticoid ...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Ramamoorthy S, Cidlowski JA Tags: Endocr Dev Source Type: research
ACTH Resistance: Genes and Mechanisms.
Abstract
ACTH resistance is a rare disorder typified by familial glucocorticoid deficiency (FGD), a genetically heterogeneous disease. Previously, genetic defects in FGD have been identified in the ACTH receptor gene (MC2R), its accessory protein (MRAP) and the steroidogenic acute regulatory protein gene (STAR). The defective mechanisms here are failures in ACTH ligand binding and/or receptor trafficking for MC2R and MRAP and, in the case of STAR mutations, inefficient cholesterol transport to allow steroidogenesis to proceed. Novel gene defects in FGD have recently been recognised in mini-chromosome maint...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Meimaridou E, Hughes CR, Kowalczyk J, Chan LF, Clark AJ, Metherell LA Tags: Endocr Dev Source Type: research
Primary generalized familial and sporadic glucocorticoid resistance (chrousos syndrome) and hypersensitivity.
Abstract
Familial or sporadic primary generalized glucocorticoid resistance or Chrousos syndrome is a rare genetic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids and a consequent hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. Primary generalized glucocorticoid hypersensitivity (PGGH) represents the mirror image of the former, and is characterized by generalized, partial, target-tissue hypersensitivity to glucocorticoids, and compensatory hypoactivation of the HPA axis. The molecular basis of both conditions has been ascribed to mutations i...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Charmandari E, Kino T, Chrousos GP Tags: Endocr Dev Source Type: research
