Endocrine Abstracts

Deoxycorticosterone (DOC: a weak mineralocorticoid) is the precursor to corticosterone (B: the major glucocorticoid in rodents) and aldosterone. Cyp11b1 encodes 11β-hydroxylase which catalyses the conversion of DOC to B in rodents. The aim of this study is to develop sensitive and specific ELISA methods to estimate urinary DOC and B levels in mice. Antibodies against DOC and B were raised in rabbits by our laboratories as previously described and HRP-Goat anti-Rabbit IgG ...

The majority of immunoassays used to measure aldosterone (most potent mineralocorticoid) levels are still based on radio-iodinated tracer, lack sensitivity and specificity and there is a definite need for their improvement. The aim of this project is to develop a highly sensitive and specific ELISA method for urinary aldosterone estimation in samples obtained from wild type and cyp11b1 knockout mice. Antibodies against aldosterone were raised in sheep as previously described. ...

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...

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...

Hyponatraemia is the commonest electrolyte disturbance among inpatients. Prompt diagnosis and management of the underlying cause is important. A 49-year-old Caucasian male presented to the emergency department with a two-day history of fever, altered mental status, vomiting, diarrhoea and postural dizziness. A rapid point of care RT-PCR test resulted positive for the SARS-CoV-2. A provisional diagnosis was presented of COVID-19 encephalopathy. The patient was usually fit and w...

Arachidonic acid (AA) metabolites derived from cytochrome P450 enzymes regulate vascular tone and renal tubular function. The cytochrome P450 4A (Cyp4A) enzymes are responsible for the synthesis of 20- hydroxyeicosatetraenoic (20-HETE), the most abundantly produced AA Cyp P450 metabolite in the kidney. Cyp4a expression and the production of 20-HETE, have been implicated in the development of hypertension. Here we have investigated the expression of various renal isoforms of Cy...

The Metabolic Syndrome (insulin resistance, hyperglycaemia, dyslipidaemia, hypertension) amplified by visceral obesity resembles Cushing's but plasma cortisol levels are not usually elevated. To explain this paradox altered tissue sensitivity to glucocorticoids has been invoked. 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) reactivates cortisone to cortisol, thus amplifying local glucocorticoid action. An adipose-selective increase in 11b-HSD1 may underlie the Metabolic S...

11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) is a key enzyme which amplifies intracellular levels of active glucocorticoids within specific tissues, including the brain. The hippocampus highly expresses both corticosteroid receptors and 11beta-HSD-1, making it a prime target for glucocorticoid actions. This brain region plays an important role in fear/anxiety behaviours and learning and memory. We examined the anxiety-related behaviours (elevated plus maze and ope...

We have created transgenic mice in which Cyp11b1, the gene encoding 11β-hydroxylase, has been knocked out. Since mice do not secrete adrenal androgens, this knockout line allows a more detailed investigation of phenotypes associated with congenital adrenal hyperplasia (CAH) without the overwhelming virilisation that characterises patients with CAH. Starting with a BAC containing the mouse Cyp11b1/b2 locus and including flanking up- and downstream sequences, a const...

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...