Endocrine Abstracts

Aldosterone is the main steroid hormone controlling sodium homeostasis in human. During the neonatal period, full term newborns and more specifically premature infants, are subjected to an impaired renal capacity to reabsorb sodium, responsible for sodium loss and failure to thrive which could be linked to a renal aldosterone unresponsiveness at birth. A clinical prospective study on 50 newborns and their mothers, revealed high aldosterone and renin levels in umbilical blood s...

Renal and cardio-vascular complications of prematurity are well established, notably those associated with renal tubular immaturity, responsible for major salt loss at birth, as well as early hypertension in adulthood. However, the molecular underlying mechanisms remain poorly understood. Our objective was to investigate the impact of preterm birth on the ontogenesis of renal corticosteroid pathways, to evaluate its implication on perinatal complications and on the emergence o...

The Mineralocorticoid Receptor (MR), a hormone-activated transcription factor that mediates sodium-retaining action of aldosterone, is highly expressed in the distal nephron in which large variations in extracellular fluid tonicity are generated by the cortico-papillary gradient. However, mechanisms regulating MR expression remain sparse. We recently showed that extracellular tonicity modulates renal MR expression through posttranscriptional mechanisms (Viengchareun, Mol Endoc...

Objective: Orexin-A and orexin-B and their G-protein coupled receptors (orexin receptor-1 & -2: OX1R, OX2R) have divergent effects on physiological behaviour, cardiovascular regulation, glucocorticoid and insulin release. Furthermore, orexins have been shown to affect both brown adipose tissue energy expenditure and thermogenesis through stimulation of sympathetic nerve activity. Despite in vivo studies demonstrating a role for orexins acting centrally on adipose ti...

Objective: Orexin-A and orexin-B and their G-protein coupled receptors (orexin receptor-1 & -2: OX1R, OX2R) have divergent effects on physiological behaviour, cardiovascular regulation, glucocorticoid and insulin release. Furthermore, orexins have been shown to affect both brown adipose tissue energy expenditure and thermogenesis through stimulation of sympathetic nerve activity. Despite in vivo studies demonstrating a role for orexins acting centrally on adipose ti...

Sex differences have been demonstrated in various biological processes such as arterial blood pressure. However, the potential sex dimorphism of the renin-angiotensin-aldosterone system and, by extension, the mineralocorticoid receptor (MR) signaling pathway, major regulators of blood pressure, has only been poorly studied, notably in the kidney. Basal systolic blood pressure (SBP) and heart rate (HR) were measured in adult male and female mice. Renal gene expression studies o...

Glucocorticoid receptor (GR or NR3C1) is a ligand-dependent transcription factor that plays an essential role in differentiation, development, inflammatory responses and energy balance and is implicated in several human diseases. Eleven germinal GR mutations have been described so far, responsible for glucocorticoid resistance with variable clinical presentation.We report original heterozygous GR mutations in three independent patients, which have been i...

Context: Surgical removal is the primary treatment option for pituitary adenomas. However, pituitary surgery is frequently incomplete because of invasion of extrasellar cerebral structures, notably, of the cavernous sinus. Our objective was to study the molecular basis of the cavernous sinus invasion by pituitary adenomas.Methods: We analyzed a tissue collection of 19 invasive pituitary adenomas with a sample from the intrasellar portion and a sample fro...

The 11-beta hydroxysteroid dehydrogenase (11βHSD) isozymes are well-known regulators of glucocorticoid hormone metabolism: 11βHSD2, mostly expressed in the distal nephron, converts cortisol [F] into cortisone [E] in humans or corticosterone into 11-dehydrocorticosterone in rodents (11-dehydro derivatives being inactive compounds), and 11βHSD1, ubiquitously expressed but predominantly in the liver, catalyzes the opposite reaction. Under pathophysiological conditi...

Primary generalized glucocorticoid resistance is characterized by glucocorticoid excess without any Cushing syndrome. Patients exhibit variable clinical presentation including arterial hypertension, hirsutism or adrenal hyperplasia. Although glucocorticoid resistance has been associated with glucocorticoid receptor (GR) mutations (encoded by NR3C1 gene), only 23 mutations have been reported so far. We have conducted a French National Research Program, referred to as M...