Endocrine Abstracts

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...

Metabolic Syndrome (visceral obesity, insulin resistance, type2 diabetes) resembles Cushing's syndrome, but lacks elevated circulating cortisol levels. This has engendered the hypothesis that excessive local glucocorticoid regeneration, resulting from elevated adipose 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) underlies the Metabolic Syndrome. We report that 11beta-HSD-1 nullizygosity (11beta-HSD-1-/-) reduced intra-adipose corticosterone levels and i...

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...

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...

Although the anti-inflammatory effects of exogenous glucocorticoids (GC) upon inflammation are well recognized, the contribution of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), an amplifier of GC action in vivo, in modulating endogenous GC action during inflammation is unknown. Mouse models of arthritis and lung inflammation were used to explore the role of 11β-HSD1 in acute and chronic inflammation. Arthritis was induced in 11β-HSD1−/&#...

The kidney plays a dominant role in long-term blood pressure (BP) control and electrolyte homeostasis but aldosterone (aldo) responsive molecular pathways in the kidney involved in regulating BP remain poorly understood despite identification of several participant genes. Many human single gene disorders affecting BP have been faithfully reproduced in mice by targeting the corresponding genes. Thus mouse is an excellent model to study molecular pathways underlying hypertension...

The pathway from aldosterone to upregulation of renal sodium re-absorption via the amiloride sensitive sodium channel (ENaC) is strongly implicated in blood pressure control and causation of hypertension (HT) in humans. In order to study these processes further an animal model is required to correlate physiological changes as hypertension develops with the molecular pathways underpinning these in kidney. Transgenic studies indicate mouse is an excellent species for modeling th...