Endocrine Abstracts

The Class A G protein-coupled receptor (GPCR), follicle-stimulating hormone receptor (FSHR), and its associated heterodimeric glycoprotein hormone (FSH) are essential for reproduction. As such, they’re key targets of assisted conception. Post-translational modification of FSH gives rise to two predominant glycosylation variants, which are modulated with ageing: partially glycosylated FSH (FSH21/18), predominates in women’s reproductive prime (20’s), displays fas...

Membrane trafficking of G-protein coupled receptors (GPCRs) is a critical mechanism by which cells mediate complex signaling pathways. Endosomes are increasingly recognized as platforms for GPCR signaling. The VEE was first identified using the LHR, a GPCR that is key in reproduction. We have shown that recycling of the LHR is driven by receptor mediated Gαs cAMP signaling from the VEE and PKA-dependent phosphorylation of the adaptor protein, APPL1, while APPL1 negatively...

Synthetic glucocorticoids are administered to pregnant women at risk of pre-term delivery to mature organs and improve neonatal survival. We have shown that glucocorticoid action is essential to mature the fetal heart. Here, we tested the hypotheses that antenatal glucocorticoid exposure, prior to the normal increase in glucocorticoid levels, will advance fetal heart maturation and this will depend on cardiovascular glucocorticoid receptor (GR).Male SMGR...

Glucocorticoids are routinely administered to pregnant women at risk of pre-term delivery to mature foetal organs and improve neonatal survival. Previous work in glucocorticoid receptor (GR)-deficient mice showed that GR activation is essential for maturation of the foetal heart. Here, we tested the hypotheses that i) antenatal glucocorticoid exposure, prior to the normal increase in glucocorticoid levels, will advance foetal heart maturation and ii) this would depend on mater...

Introduction: Humans with glucocorticoid receptor (GR) deficiency and global heterozygous GR knockout (GR+/−) show compensatory activation of the hypothalamic-pituitary-adrenal axis, resulting in salt-sensitive hypertension due to increased mineralocorticoid activity. Previous studies suggest renal mechanisms, including changes in cell proliferation, gene expression and electrolyte transport, may contribute to this phenotype but underlying adaptive adrenal responses have...

Variation in the human glucocorticoid receptor (GR) gene associates with relative glucocorticoid resistance, hypertension and increased cardiovascular disease risk. Mice heterozygous for a null GR mutation (GR+/−) are also glucocorticoid resistant with raised circulating glucocorticoid levels and elevated blood pressure in adulthood. We have characterised the cardiac phenotype of these mice throughout development and investigated their response to cardiovascul...

Variation in the glucocorticoid receptor (GR) gene associates with relative glucocorticoid resistance, hypertension and increased cardiovascular disease risk in humans. To investigate the contribution of cardiac GR to this phenotype we have characterised adult male mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO) and have found left ventricular function to be impaired.SMGRKO mice, generated by crossing GR ‘floxed’ mice...

Salt-sensitive hypertension is a major risk factor for cardiovascular morbidity. Humans and mice with glucocorticoid receptor haploinsufficiency (GR+/−) are hypertensive, which in mice reflects activation of the renin-angiotensin-aldosterone system. Furthermore, glucocorticoid receptor (GR) gene polymorphisms associate with increased cardiovascular disease risk. Here we investigated the effect of dietary salt intake on blood pressure, heart and kidney in GR+/− mice...

Specific variations in the human glucocorticoid receptor (GR) gene associate with increased cardiovascular disease risk. GR signalling is essential for cardiac maturation in utero and adult mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice) have cardiac hypertrophy, fibrosis and impaired function. Intriguingly, levels of left ventricle (LV) mRNA encoding the mineralocorticoid receptor (MR), which is pro-fibrotic in heart, rise postnatally ...