Endocrine Abstracts

Small cell lung cancer (SCLC) is highly aggressive with a particularly poor prognosis. This is due to tumours quickly metastasising and developing chemoresistance. SCLC tumours possess neuroendocrine properties in that they secrete prohormones such as pro-opiomelanocortin (POMC) and pro-gastrin releasing peptide (pro-GRP). These can be detected in the circulation and therefore have potential as biomarkers for prognosis and relapse. The aims of this study are; i) develop a mode...

Alternative promoters control many genes including prolactin (PRL), which in man is expressed at extra-pituitary sites controlled by an alternative promoter located 5.8 Kbp upstream of the pituitary transcription start site. Previous studies using short promoter fragments may be misleading, as the human hPRL genomic locus has many conserved far-upstream regions. To study the function of the alternative promoter, we engineered a bacterial artificial chromosome (BAC) expressing ...

Gene expression in living cells is dynamic and unstable, and fluctuations in transcription may be subject to stochastic regulation of processes including transcription factor and polymerase recruitment, and chromatin remodelling. One gene that has been shown to display dynamically variable transcription and marked heterogeneity between cells is prolactin (PRL). Time-lapse imaging of PRL-reporter gene expression in single rat pituitary GH3 cells revealed distinct long-term tran...

Pituitary development, in particular the differentiation of anterior pituitary endocrine cells, remains to be fully understood, and may have implications for adult pituitary plasticity and hyperplasia. We have used prolactin-reporter transgenic rats to characterise prolactin transcription during the appearance of newly formed lactotroph cells during fetal development.Transgenic rats with the firefly luciferase reporter gene inserted into exon 1b of a 160...

Prolactin (PRL) is a hormone mainly produced by the lactotroph cells of the anterior pituitary gland. Besides its pivotal role in reproduction, PRL has also been found to have immuno-modulatory properties. The pituitary is the main source of circulating PRL, however it is also expressed in humans at extra-pituitary sites1. In extra-pituitary tissues, PRL mRNA contains an extra exon (exon 1a), and expression is regulated by an alternative promoter upstream of the pit...

Background: Adult growth hormone deficient (AGHD) is associated with reduced bone turnover and reduced bone mineral density (BMD): factors improved by growth hormone replacement (GHR). Obesity is associated with reduced bone turnover but increased BMD. We investigated the impact of body mass index on parathyroid hormone (PTH), phospho-calcium metabolism and bone turnover in AGHD patients before and after GHR.Study design: Of 31 AGHD patients (15 obese pa...

3-iodothyronamine (T1AM) is a novel, endogenous rapid acting biogenic amine, which is a potent agonist of the G-protein coupled trace amine-associated receptor 1, TAAR1. It has been suggested that endogenous T1AM could be generated by enzymatic deiodonation and decarboxylation of T4. The presence of T1AM in rat brain and the distribution of the TAAR1 receptor in the hypothalamus suggest that T1AM may affect food intake and regulate e...

Nuclear Receptors control many developmental and physiological processes by regulating the expression of networks of genes. Their ability to activate or repress gene transcription depends on the recruitment of coactivators and corepressors that function as scaffolds for the binding of chromatin remodelling enzymes. RIP140 is a ligand dependant corepressor for most, if not all, nuclear receptors with key roles in energy homeostasis and reproduction.RIP140...

Agouti-related protein (AGRP) plays a key role in energy homeostasis with the carboxy-terminal domain acting as an endogenous antagonist of the melanocortin-4 receptor (MC4-R). It has been suggested that the amino-terminal domain of AGRP binds to syndecan-3, allowing it to regulate local concentrations of AGRP at the MC4-R. This model assumes that AGRP is secreted as a full-length peptide. However, AGRP contains several consensus prohormone convertase cleavage sites: Lys52-Lys...

BACKGROUND: Adult Growth Hormone Deficiency (AGHD) is associated with reduced bone mineral density (BMD). PTH plays an important role in bone metabolism and reports have suggested target cell insensitivity to PTH as a contributor to the changes in bone turnover seen in AGHD. Although growth hormone replacement (GHR) increases BMD, the underlying mechanisms remain unclear.OBJECTIVES: To determine the effect of GHR on 24-hour PTH profiles, phosphocalcium ...