Endocrine Abstracts

Mice with congenital adrenal hyperplasia due to a null mutation of cyp11b1, the gene encoding the steroidogenic enzyme 11β-hydroxylase, have low glucocorticoid levels, reduced adiposity and increased liver weight. It is notable that null mice are also glucose intolerant. Here, we have investigated these phenotypes in more detail. Plasma corticosterone levels were less responsive to restraint stress and cholesterol and triglyceride levels were not significantly different i...

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...

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...

Deficiency of the intracellular glucocorticoid (GC) reactivating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) invokes compensatory activation of the HPA axis. Nevertheless, 11β-HSD1−/− mice resist dietary-induced obesity indicating that target tissues are protected from GC actions. Since endocrine adaptation to diet is mediated by altered HPA activity, we investigated whether the adrenal response to high fat (HF) diet is compr...

Steroidogenic cells of the adrenal cortex are thought to originate from a peripherally-located self-renewing population of undifferentiated stem or progenitor cells. These cells divide infrequently to give daughters, which proliferate transiently (termed transiently amplifying (TA) cells), migrate and differentiate to replenish the functionally-differentiated zones of the adrenal cortex, or remain in situ as undifferentiated stem cells. Theoretically such stem cells can...

Previously, we have shown that 5α-tetrahydrocorticosterone (5αTHB), the reduced metabolite of corticosterone (B, the main glucocorticoid in rodents), binds to the glucocorticoid receptor, suppresses the HPA axis but has weak in vivo effects on adipose tissue and liver metabolism. Here we have compared the anti-inflammatory effects of B and 5αTHB in three in vitro and in vivo experiments. Cytokine release was measured by cytometric bead array...

Hypertension in obese Zucker rats is associated with raised plasma aldosterone, suppressed renin and increased hypothalamo–pituitary–adrenal activity. We investigated the possible causes and consequences of these associations by comparing adrenal gene expression and urinary electrolyte and steroid excretion patterns in lean and obese rats. Groups (n=11) of adult male lean and obese Zucker rats were held in metabolism cages for 7 days. Urine collected over the ...

Glycyrrhetinic acid (GA) has diverse in vitro effects as an inhibitor of 11beta hydroxysteroid dehydrogenase (11HSD), 5alpha reductase and hormone receptor binding. However, in vivo GA studies have focussed on the hypertensive effects associated with the syndrome of apparent mineralocorticoid excess (SAME) in which 11HSD inhibition allows glucocorticoid hormones to bind inappropriately to MR and subsequent decreased aldosterone synthesis. Here we consider whether...

Obesity, particularly abdominal (visceral) obesity, is a major risk factor for development of the metabolic syndrome. Human and animal studies have shown elevated intra-adipose glucocorticoid-action in obesity and suggest that increased glucocorticoid receptor (GR) density may be an important determinant of visceral adiposity. We have tested this hypothesis in transgenic (Tg) mice in which adipose GR levels have been increased or decreased, by expression of “sense” o...

Inactivating mutations of the POMC gene in humans and mice result in a complex phenotype of hyperphagia, obesity and glucocorticoid (GC) deficiency, but without many features of metabolic syndrome. We have previously shown that replacement of GC in Pomc−/− mice exacerbates their hyperphagia, increases fat mass and elevates plasma leptin and insulin. We have now examined key determinants of glucocorticoid action, including glucocorticoid receptor (...