Abstract:
:Twenty-five years have elapsed since the calcium-sensing receptor (CaSR) was first identified in bovine parathyroid and the receptor is now recognized as a fundamental contributor to extracellular Ca2+ (Ca2+ e) homeostasis, regulating parathyroid hormone release and urinary calcium excretion. The CaSR is a class C G-protein-coupled receptor (GPCR) that is functionally active as a homodimer and couples to multiple G-protein subtypes to activate intracellular signalling pathways. The importance of the CaSR in the regulation of Ca2+ e has been highlighted by the identification of >400 different germline loss- and gain-of-function CaSR mutations that give rise to disorders of Ca2+ e homeostasis. CaSR-inactivating mutations cause neonatal severe hyperparathyroidism, characterised by marked hypercalcaemia, skeletal demineralisation and failure to thrive in early infancy; and familial hypocalciuric hypercalcaemia, an often asymptomatic disorder associated with mild-moderately elevated serum calcium concentrations. Activating mutations are associated with autosomal dominant hypocalcaemia, which is occasionally associated with a Bartter's-like phenotype. Recent elucidation of the CaSR extracellular domain structure enabled the locations of CaSR mutations to be mapped and has revealed clustering in locations important for structural integrity, receptor dimerisation and ligand binding. Moreover, the study of disease-causing mutations has demonstrated that CaSR signals in a biased manner and have revealed specific residues important for receptor activation. This review presents the current understanding of the genetic landscape of CaSR mutations by summarising findings from clinical and functional studies of disease-associated mutations. It concludes with reflections on how recently uncovered signalling pathways may expand the understanding of calcium homeostasis disorders.
journal_name
J Mol Endocrinoljournal_title
Journal of molecular endocrinologyauthors
Gorvin CMdoi
10.1530/JME-19-0104subject
Has Abstractpub_date
2019-08-01 00:00:00pages
R1-R16issue
2eissn
0952-5041issn
1479-6813pii
JME-19-0104.R1journal_volume
63pub_type
杂志文章,评审abstract::Abnormal placental function is well-established as a major cause for poor pregnancy outcome. Placental blood flow within the maternal uteroplacental compartment, the fetoplacental circulation or both is a vital factor in mediating placental function. Impairment in flow in either or both vasculatures is a significant r...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-17-0139
更新日期:2018-01-01 00:00:00
abstract::This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-19-0186
更新日期:2020-02-01 00:00:00
abstract::The angiotensin II (Ang II) type 2 receptor (AT(2)) is a member of the seven-transmembrane domain, G-protein coupled receptor family. This receptor is ubiquitously distributed in the fetus but, in most tIssues, its expression dramatically falls in the first few hours after birth. Based on this observation, the hypothe...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1677/jme.0.0310359
更新日期:2003-12-01 00:00:00
abstract::The effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3; 10 nmol/l) on the human monomyelocytic cell line U937 were investigated. Addition of 1,25-(OH)2D3 led to a decrease in cell proliferation which fell at 72 h to 67.8 +/- 4.3% (mean +/- S.E.M.) of control values. The presence of CD14, a surface marker found on matur...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0030043
更新日期:1989-07-01 00:00:00
abstract::MicroRNAs are endogenous, conserved, and non-coding small RNAs that function as post-transcriptional regulators of fat development and adipogenesis. Adipogenic marker genes, such as CCAAT/enhancer binding protein α (Cebpa), peroxisome proliferator-activated receptor γ (Pparg), adipocyte fatty acid binding protein (Ap2...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-14-0013
更新日期:2014-06-01 00:00:00
abstract::We studied the effect of adenosine on prolactin secretion by the anterior pituitary, and the transduction mechanisms whereby the purine exerts its action. Adenosine inhibited prolactin release in basal and in vasoactive intestinal peptide (VIP)- or TRH-stimulated conditions. Pertussis toxin pretreatment reduced the in...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0110325
更新日期:1993-12-01 00:00:00
abstract::Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid gland in response to changes in ionized calcium (Ca(2+)) concentrations. In this study, we measured PTH secretion, and PTH mRNA and calcium-sensing receptor (CaR) mRNA expression by equine parathyroid chief cells in vitro. We also evaluated th...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0310609
更新日期:2003-12-01 00:00:00
abstract::Tamoxifen acts as an oestrogen antagonist in the breast reducing cell proliferation, but in the uterus as an oestrogen agonist resulting in increased cell proliferation. Tamoxifen exerts its tissue-specific effects through the oestrogen receptors (ERalpha or ERbeta). The levels and functions of the two ERs affect the ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01784
更新日期:2005-12-01 00:00:00
abstract::Pancreatic beta-cells are responsible for producing all of the insulin required by an organism to maintain glucose homeostasis. Defects in development, maintenance, or expansion of beta-cell mass can result in impaired glucose metabolism and diabetes. Thus, identifying the molecular regulators of these processes may p...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1677/JME-06-0053
更新日期:2007-02-01 00:00:00
abstract::Reproductive hormone imbalance in infertile women is correlated to high levels of phthalates and alkylphenols, which are among endocrine-disrupting chemicals (EDCs). Previous studies have shown that they interfere with gene expression by deregulating levels of microRNAs (miRs), small non-coding RNAs targeting mRNAs en...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-20-0149
更新日期:2020-11-01 00:00:00
abstract::The genomic structure and transcriptional regulation of the rat apelin receptor (APJR) were analysed by rapid amplification of 5' cDNA ends (5'-RACE), transient expression assays and DNA-protein interaction. Analysis of the 5'-flanking region of a rat genomic clone shows no TATA box, but a putative CAAT box and severa...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01927
更新日期:2006-02-01 00:00:00
abstract::Both 17beta-estradiol and prolactin play important roles in the mammary gland, raising the possibility of functional cross-talk between the two signaling pathways. Here, we demonstrate that estrogen receptor-alpha (ERalpha) and -beta (ERbeta) are both able to potentiate transcription from a Stat5-responsive promoter w...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0270093
更新日期:2001-08-01 00:00:00
abstract::Human 3beta-hydroxysteroid dehydrogenase/steroid Delta(5)-Delta(4)-isomerase (3beta-HSD/isomerase) is a bifunctional, single enzyme protein that is membrane-bound in the endoplasmic reticulum (microsomes) and mitochondria of cells in the placenta (type I) and in the adrenals and gonads (type II). Two membrane-binding ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0230231
更新日期:1999-10-01 00:00:00
abstract::A full-length transcript encoding a functional lamprey glycoprotein hormone receptor I (lGpH-R I, GenBank AY750688) was cloned from the testes of the sea lamprey, Petromyzon marinus, using the GpH-R protein fingerprint GLYCHORMONER from the PRINTS database. The present study is the first to identify a GpH-R transcript...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.02064
更新日期:2006-08-01 00:00:00
abstract::A prolactin cDNA was cloned from a cDNA expression library constructed from total RNA of bullfrog (Rana catesbeiana) adenohypophyses by immunoscreening with antiserum against bullfrog prolactin. The cDNA clone thus obtained contained a 249 bp insert. Using this clone as a probe, plaque hybridizations were performed an...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0050281
更新日期:1990-12-01 00:00:00
abstract::Glucocorticoid and androgen receptors have been shown to function through the same palindromic glucocorticoid response element (GRE) and yet have differential effects on gene transcription. In this study, we examined the functional and structural relationship of the androgen and glucocorticoid receptors with the andro...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0220313
更新日期:1999-06-01 00:00:00
abstract::Whether insulin, at physiological concentrations, has direct effects on vascular smooth muscle cells (VSMCs) remains controversial. Our aim was to characterize the mechanism for insulin resistance in VSMCs. For comparison, the effects of IGF1 and IGF2 were also studied. Cultured human aortic smooth muscle cells (HASMC...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-09-0021
更新日期:2009-12-01 00:00:00
abstract::The hormone human chorionic gonadotrophin (hCG) shows extensive sequence homology with LH. Thus, many of the antigenic epitopes on hCG are shared with LH, leading to immunological cross-reaction between these two hormones. Anti-fertility and anti-cancer vaccines based upon hCG should ideally target only the hCG-specif...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0320571
更新日期:2004-04-01 00:00:00
abstract::We have cloned a full length cDNA coding for the activin type IIB receptor (GactRIIB) from the goldfish ovary. GactRIIB shares 73 and 70% amino acid identity in the extracellular domain, and 78 and 80% identity in the intracellular domain with the type IIB receptors of the mouse and Xenopus respectively. The intracell...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0190047
更新日期:1997-08-01 00:00:00
abstract::Murine double minute clone 2 (MDM2) is a multifunctional protein, which modulates nuclear receptor-mediated transactivation. In this study, we show that MDM2 significantly enhanced estrogen receptor α (ERα) and ERα/specificity protein-mediated transactivation in MCF-7 and ZR-75 breast cancer cells. This was demonstrat...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-10-0110
更新日期:2011-02-15 00:00:00
abstract::Secretion of parathyroid hormone-related protein (PTHrP) by sheep fetal parathyroid glands is reported to be an important factor in the maintenance of a placental calcium pump. The aim of the present study was to determine whether the developing rat parathyroid glands express PTHrP or parathyroid hormone (PTH), or bot...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0170149
更新日期:1996-10-01 00:00:00
abstract::Ovarian cortical tissue cryopreservation is a relatively novel approach to preserving fertility in women diagnosed with cancer. However, the effects of freezing-thawing are not fully understood, mainly due to the lack of suitable methods to assess tissue's survival after thawing. Disparities in steroid production have...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-18-0237
更新日期:2019-03-01 00:00:00
abstract::Progesterone's ability to maintain pregnancy in eutherian mammals highlighted this steroid as the 'hormone of pregnancy'. It was the unique 'pro-gestational' bioactivity of progesterone that enabled eventual purification of this ovarian steroid to crystalline form by Willard Myron Allen in the early 1930s. While a fun...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-19-0212
更新日期:2020-07-01 00:00:00
abstract::Insulin-like growth factor-I (IGF-I) analogues were produced with the aim of identifying IGF-I residues that contribute to the specificity of binding to the type 1 IGF receptor as opposed to the insulin receptor. Receptor binding properties of a series of A- and B-domain analogues were compared using rat L6 myoblasts,...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0170237
更新日期:1996-12-01 00:00:00
abstract::The nona-peptide oxytocin (OT) induces contraction of the myometrium by interaction with specific plasma membrane associated OT receptors (OTR), whereas stimulation of beta2-adrenoceptors (beta2AR) causes relaxation. Homologous desensitization of the myometrium to both hormones has been described. However, a possible ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0200261
更新日期:1998-04-01 00:00:00
abstract::The effect of steroid hormone treatment on coho salmon (Oncorhynchus kisutch) was examined. The cDNAs for coho salmon FSH beta and LH beta subunits were cloned and sequenced using reverse transcriptase PCR. Northern blot analysis revealed that a single transcript of 1 kb for each of these subunits was present in the p...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0210291
更新日期:1998-12-01 00:00:00
abstract::The diagnosis of conventional and oncocytic poorly differentiated (oPD) thyroid carcinomas is difficult. The aim of this study is to characterise their largely unknown miRNA expression profile and to compare it with well-differentiated thyroid tumours, as well as to identify miRNAs which could potentially serve as dia...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-13-0266
更新日期:2014-03-06 00:00:00
abstract::The monocarboxylate transporter 8 (MCT8) is a member of the major facilitator superfamily (MFS). These membrane-spanning proteins facilitate translocation of a variety of substrates, MCT8 specifically transports iodothyronines. Mutations in MCT8 are the underlying cause of severe X-linked psychomotor retardation. At t...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-14-0272
更新日期:2015-02-01 00:00:00
abstract::Previous studies have shown that, in unstimulated mammary epithelial cells from virgin mice, prolactin receptors are retained intracellularly because of their incomplete N-glycosylation. Activation of the nitric oxide/cGMP pathway stimulates Nacetylglucosamine (NAG) transferase I activity, completion of terminal glyco...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0240377
更新日期:2000-06-01 00:00:00
abstract::Bisphenol A (BPA) is a xenobiotic endocrine-disrupting chemical. In vitro and in vivo studies have indicated that BPA alters endocrine-metabolic pathways in adipose tissue, which increases the risk of metabolic disorders and obesity. BPA can affect adipose tissue and increase fat cell numbers or sizes by regulating th...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-14-0282
更新日期:2015-06-01 00:00:00