Searchable abstracts of presentations at key conferences in endocrinology

ea0013p191 | Diabetes, metabolism and cardiovascular | SFEBES2007

Renal effects of ACTH: functional and microarray studies in the mouse

Kenyon Christopher , Mullins Linda , Dunbar Donald , Mullins John , Bailey Matthew

We investigated ACTH-induced hypertension in mice by studying renal function in vivo and by analysing renal gene expression by microarray and RT PCR methods. During two weeks sc infusion with Synacthen, mean blood pressure in adult male mice increased (89±5 vs 110±2 mmHg), and plasma corticosterone, adrenal weights and drinking rate increased by 5, 2 and 2.5-fold respectively (P<0.01); renal mass was unaffected. Greater mineralocorticoid activity wa...

ea0032p336 | Developmental Endocrinology | ECE2013

Effects of pharmacological and genetic manipulation of glucocorticoids during early development of the zebrafish embryo

Wilson Kathryn , Matrone Gianfranco , Tucker Carl , Hadoke Patrick , Kenyon Christopher , Mullins John , Denvir Martin

Background: The effects of glucocorticoids (GC) on the developing zebrafish embryo (Zfe) are poorly characterised. We have assessed the effects of pharmacological and genetic manipulation of cortisol and glucocorticoid receptors (GR) on global development and stress response during the first 120 hpf.Methods: Cortisol production was modulated by inhibiting the enzyme 11b hydroxylase using morpholino gene knockdown (MO) or incubation in the drug metyrapone...

ea0028p290 | Reproduction | SFEBES2012

Uterine cell turnover in a mouse model of adenomyosis caused by congenital adrenal hyperplasia

Sadraie Maryam , Hastings Julie , Mullins Linda , Mullins John , Morley Steven , Kenyon Christopher

We have investigated cell proliferation and apoptosis in Cyp11b1 null (ko) mice. Reduced glucocorticoid (corticosterone) synthesis in ko mice is associated with increased progesterone and deoxycorticosterone and the development of adenomyosis. Numbers of putative uterine stem cells were assessed in wild type (wt) and ko at an age (10–12 months) when the onset of adenomyosis was considered imminent. Mice were infused with bromodeoxyuridine (BrdU) for seven days then killed...

ea0025p281 | Reproduction | SFEBES2011

HRPE773 (ZG16B) expression is elevated in human endometrium during the early secretory phase of the menstrual cycle and in uterine decidua following miscarriage

Ng Bonnie , McDonald Sarah , Ren Xia , Mullins John , Rae Michael , Critchley Hillary , Horne Andrew , Morley Steven

Introduction: Expression of murine CSP-1/Dcpp secretory proteins was first identified in sublingual salivary glands and subsequently in secretory epithelia of several other tissues, including the mouse female reproductive tract where expression is regulated by oestrogen. Preliminary studies indicated that HRPE773, the human CSP-1/Dcpp orthologue, displayed a similar pattern of expression to its murine counterparts. We therefore hypothesized that HRPE773 might be expressed in h...

ea0021oc3.2 | Young Endocrinologists prize session | SFEBES2009

β-Cell specific overexpression of 11β-hydroxysteroid dehydrogenase type 1 reverses high fat diet-induced β-cell failure

Turban-Rajaonah Sophie , Liu Xiaoxia , Ramage Lynne , Mullins John J , Seckl Jonathan R , Morton Nicholas M

Insulin-resistant diabetes is characterised by progressive pancreatic β-cell dysfunction. Elevated pancreatic islet activity of the intracellular glucocorticoid amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) was hypothesized to drive this process in genetically obese rodents. To determine the direct effects of elevated 11β-HSD1 on β-cell function in diabetes in vivo we created a transgenic model overexpressing 11β-HSD1...

ea0015oc8 | Young Endocrinologist prize session | SFEBES2008

β-cell 11β-Hydroxysteroid dehydrogenase type 1 contributes to type 2 diabetes

Turban Sophie , Ramage Lynne , Paterson Janice , Mullins John , Seckl Jonathan , Morton Nik

High systemic cortisol levels contribute to insulin resistance and may exacerbate the development of diabetes by impairing the insulin secretory response of the pancreatic beta-cells (β-cells). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key modulator of glucocorticoid effect within target tissues and high adipose or liver levels of this enzyme may contribute to obesity and/or metabolic disease. We investigated cellular localization of 11β-HSD1 ...

ea0028p240 | Pituitary | SFEBES2012

Transcriptional regulation of prolactin in the rat oestrous cycle

Patist Amanda , Featherstone Karen , Spiller David , Semprini Sabrina , McNeilly Judith , McNeilly Alan , Mullins John , White Michael , Davis Julian

Circulating levels of prolactin are subject to acute and long-term regulation by many factors including oestrogen and dopamine. We have studied the regulation of prolactin promoter activity in living pituitary cells using transgenic Fischer rats in which reporter gene expression is regulated by the human prolactin gene locus (hPRL-d2EGFP). We have previously identified pulsatile prolactin transcription patterns in living lactotroph cells in fetal tissue, that became stabilised...

ea0025p244 | Pituitary | SFEBES2011

BAC recombineering to understand the role of the alternative promoter in the regulation of prolactin expression

Awais Raheela , McNamara Anne , Harper Claire , Adamson Anthony , Spiller Dave , Semprini Sabrina , Mullins John , Davis Julian , White Michael R H

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 ...

ea0021p293 | Pituitary | SFEBES2009

Long-term unsynchronised transcriptional cycles in individual living pituitary cells

Harper Claire , Finkenstadt Barbel , Woodcock Dan , Friedrichsen Sonke , Semprini Sabrina , Spiller Dave , Mullins John , Rand David , Davis Julian , White Mike

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...

ea0021p298 | Pituitary | SFEBES2009

Onset of prolactin gene transcription in nascent pituitary lactotroph cells

Featherstone Karen , Harper Claire , McNamara Anne , Semprini Sabrina , Spiller David , McNeilly Alan , Mullins John , White Michael , Davis Julian

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...