Pseudohypoaldosteronism.
Abstract
Pseudohypoaldosteronism (PHA) is a rare syndrome of mineralocorticoid resistance. PHA type 1 (PHA1) can be divided into two different forms, showing either a systemic or a renal form of mineralocorticoid resistance. The first is caused by mutations of the genes coding the epithelial sodium channel, the latter is caused by mutations in the mineralocorticoid receptor coding gene NR3C2. The clinical manifestation of systemic PHA1 is overt dehydration and hyponatremia due to systemic salt loss and severe hyperkalemia. The leading clinical sign of the less severe renal PHA1 is insufficient weight gain ...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Riepe FG Tags: Endocr Dev Source Type: research
New Aspects of the Physiology of the GH-IGF-1 Axis.
Abstract
Growth hormone (GH) secretion from the pituitary is regulated by a complex network of CNS and peripheral inputs. Circulating GH binds to its receptor and initiates a cascade of signaling events which involve the JAK2-STAT pathway, the PI3K/Akt pathway and the RAS/MAPK pathway, leading to the transcription of several genes, including insulin-like growth factor 1 (IGF-1), IGFBP3, ALS, and others. Recent findings indicate that nutrition plays an important role in GH secretion and action. Furthermore, data are emerging which suggest that the RAS-MAPK pathway as well as epigenetic regulation of transcr...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Vottero A, Guzzetti C, Loche S Tags: Endocr Dev Source Type: research
Molecular and Clinical Aspects of GHRH Receptor Mutations.
Abstract
The growth hormone (GH)-releasing hormone (GHRH) receptor (GHRHR) belongs to the G protein-coupled receptor family. It binds GHRH resulting in somatotroph cell proliferation and stimulation of GH secretion. Mutations in the gene encoding for GHRHR (GHRHR, OMIM No. 139191) are being reported with increasing frequency in familial isolated GH deficiency. To date, the reported GHRHR mutations include eight missense, seven splice, three microdeletions, and two non-sense mutations. One promoter mutation has also been reported. Most of these mutations show a recessive mode of inheritance. The phenotype i...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Corazzini V, Salvatori R Tags: Endocr Dev Source Type: research
Current Issues on Molecular Diagnosis of GH Signaling Defects.
Abstract
The growth-promoting effects of GH are mediated primarily by regulating the biosynthesis of insulin-like growth factor (IGF)-1. The binding of circulating GH to the cell surface GH receptor (GHR) initiates signaling cascades, of which the signal transducer and activator of transcription (STAT)-5b pathway has proven, in both rodent models and human case studies, to be the most critical in regulating IGF-1 production. The identification of rare inactivating STAT5B mutations in children, whose severe postnatal growth retardation was associated with GH insensitivity (GHI) and IGF-1 deficiency, confirm...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Feigerlova E, Hwa V, Derr MA, Rosenfeld RG Tags: Endocr Dev Source Type: research
Molecular IGF-1 and IGF-1 Receptor Defects: From Genetics to Clinical Management.
Abstract
Molecular defects of the insulin-like growth factor 1 gene (IGF1) are rare in the human. Only three homozygous and two families with heterozygous mutations of the IGF1 gene have been described, resulting in a variable degree of intrauterine and postnatal growth retardation, microcephaly, developmental delay and deafness. Detailed genetic analysis and functional experiments have shown that IGF-1 plays a key role in pre- and postnatal growth and development in human. Eleven patients with heterozygous and 2 patients with compound heterozygous mutations in the type 1 IGF1 receptor gene (IGF1R) have be...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Walenkamp MJ, Losekoot M, Wit JM Tags: Endocr Dev Source Type: research
Phenotypes, Investigation and Treatment of Primary IGF-1 Deficiency.
Abstract
GH insensitivity, also known as primary IGF-1 deficiency (PIGFD), presents as growth failure, and in its severe form is associated with dysmorphic and metabolic abnormalities. PIGFD is caused by genetic defects in the GH-IGF-1 axis. The field of PIGFD due to mutations affecting GH action has evolved since the original description of the extreme phenotype related to homozygous GH receptor mutations over 40 years ago. A continuum of genetic, phenotypic, and biochemical abnormalities can be defined associated with clinically relevant defects in linear growth. A systematic protocol of investigation as...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Savage MO Tags: Endocr Dev Source Type: research
Human congenital perilipin deficiency and insulin resistance.
Abstract
Lipid droplets (LDs) can form in all eukaryotic cells, but white adipocytes are uniquely adapted to store energy as neutral lipid within a large unilocular LD. Non-esterified fatty acids can then be released from the LD store by lipases for use in oxidative tissues. Perilipin was the first mammalian LD protein to be identified in adipocytes where it plays a key role in co-ordinating access of lipases to the core triacylglycerol. We recently identified the first human loss-of-function mutations in PLIN1 in patients with a novel form of familial partial lipodystrophy, severe insulin resistance, diab...
Source: Endocrine Development - February 10, 2013 Category: Endocrinology Authors: Kozusko K, Patel S, Savage DB Tags: Endocr Dev Source Type: research
