Endocrine Abstracts

We present data on open reading frame 62 encoded on human chromosome 6 (C6orf62), a gene whose protein expression and function has not been described to date. The gene product of C6orf62 was designated pituitary associated regulator of hormone secretion (PARS).Initial gene expression screens showed that PARS transcription is differentially regulated in secreting and non-secreting pituitary adenomas, as well as in normal pituitary tissue. Inspired ...

Objective: The human androgen recteptor (AR) contains a polyglutamine and a polyglycine stretch that are highly polymorphic and are coded by a CAG and GGN repeat, respectively, in exon 1 of the AR gene. Although in vitro studies indicated a possible effect on AR gene tanscription and clinical observations suggest a modulation of androgen action, the functional significance of the GGN repeat remains unclear.We wanted to assess whether the GGN repea...

The endoplasmic reticulum (ER) is a cellular compartment specialized for chaperone-assisted folding and post-translational modification of nascent polypeptides. Disruption of ER homeostasis leads to accumulation of unfolded protein and activation of the unfolded protein response (UPR). The UPR emanates from the ER through activation of three transmembrane sensors, IRE1, PERK, and ATF6. IRE1 is a protein kinase / endoribonuclease that, upon activation, initiates a splicing reac...

All metabolites in the body are in a state of constant flux, and changes in their levels may reflect either increased rate of production or decreased clearance, or both. Stable isotope technology can be used in physiological studies to determine mechanisms mediating changes in metabolites. For example, the decline in blood glucose following administration of insulin could be due to either increased uptake into peripheral tissues, or (as is the case) by suppression of hepatic g...

GCMB, which is the mammalian homologue of the Drosophila gene Glial cells missing, encodes a 506 amino acid parathyroid-specific transcription factor that contains: a GCM DNA-binding domain at residues 19–176; a predicted nuclear localization signal (NLS) at residues 176–193; an inhibitory domain at residues 258–347; and two transactivation domains at residues 174–263, and residues 428–506. To date only six different GCMB mu...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder of mineral metabolism that is characterized by lifelong elevation of serum calcium concentrations associated with inappropriately low urinary calcium excretion (calcium clearance:creatinine clearance <0.01). Three separate FHH loci have been identified (FHH1-3). Loss-of-function mutations of the calcium-sensing receptor (CaSR) gene located on 3q21.1, which account for the majority of FHH c...

Pituitary tumor transforming gene binding factor (PBF) is a relatively uncharacterized gene implicated in endocrine neoplasia. Given the presence of putative oestrogen response elements (ERE) in its promoter, we assessed PBF regulation by oestrogen. PBF mRNA expression was induced maximally at 48 h by 20 nM diethylstilbestrol in ERalpha-positive MCF-7 cells (2.1±0.1-fold, P<0.001, N=6). PBF protein expression levels were also significantly up-regulated b...

GATA3 mutations cause the congenital autosomal dominant hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome. GATA3 belongs to a family of dual zinc-finger nuclear transcription factors that recognise the consensus (A/T)GATA(A/G) motif and are involved in vertebrate embryonic development. To date, the mechanisms by which GATA3 mutations lead to haploinsufficiency of the GATA3 protein, which comprises 444 amino acids, have been shown to include loss of ...

GLUT8 is a class 3 sugar transport facilitator, and transports glucose with high affinity (km~2 mM). GLUT8 mRNA is expressed in brain, heart, skeletal muscle, adipose tissue, adrenal gland, liver and at particulary high levels in testis. In testis, the GLUT8 protein is located in an intracellular compartment of spermatocytes, spermatids and mature spermatozoa. GLUT8 contains an N-terminal dileucine sorting signal retaining the transporter in an intracellular compartment. So fa...

The initiation of mammalian puberty requires an increased pulsatile release of gonadotrophin hormone releasing hormone (GnRH) from the hypothalamus. This increase is brought about by changes in transsynaptic and glial–neuronal communication. Coordination of this regulatory neuronal–glial network likely requires the participation of a multiplicity of genes hierarchically arranged within discrete, but interactive, networks. The identity and structural features of at le...