Endocrine Abstracts

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...

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...

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...

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...

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...

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 ...

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...

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...