Endocrine Abstracts

Aldosterone exerts numerous pleiotropic functions, notably in the kidney where it controls hydroelectrolytic homeostasis and ultimately blood pressure. Aldosterone acts by activating the mineralocorticoid receptor (MR), a transcription factor that regulates target gene expression. Alteration of the mineralocorticoid signaling leads to various diseases including hypertension, cardiovascular, renal, metabolic or CNS disorders.Aldosterone mechanism of actio...

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...

Mitotane (o,p’DDD) represents the most effective treatment of adrenocortical carcinoma (ACC). However, molecular mechanisms of mitotane action remain poorly understood. Mitochondrial (mt) impact of mitotane has previously been suggested but not yet fully validated. We investigated functional consequences of mitotane exposure on mitochondrial steroidogenesis, respiratory chain activity and biogenesis, using human adrenocortical secreting H295R and non-secreting SW13 cells....

Glucocorticoid resistance syndrome, a rare genetic disease, is often associated with glucocorticoid receptor (GR) loss-of-function mutations. Six patients carrying heterozygous mutations of NR3C1 gene encoding GR, either missense R477S, Q501H, L672P or non-sense R469X, R491X, Y660X mutations were studied. Surprisingly, NR3C1 mutation carriers presented with low kalemia, low plasma renin and aldosterone levels associated or not with arterial hypertension, cons...

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...

Introduction: Testicular morphology and immunohistochemistry have never been reported in genetically documented adult patients with 5α-reductase type 2 deficiency (5α-R2 deficiency).Case report: We describe the testicular histopathology of a 17-year-old XY female with primary amenorrhea, failure of pubertal breast development, virilization, clitoromegaly, and bilateral cryptorchidism (testes located in the inguinal canals). The diagnosis of 5&#...

Premature ovarian insufficiency (POI) is a disorder which affects ~1% of women under 40 years of age. Genetic component has been suggested in the majority of cases of nonsyndromic forms, and recently mutations of NR5A1 have been reported to be associated with POI. In order to evaluate the frequency of NR5A1 mutations in POI together with the functional characterisation of the existing variants, we conducted a genetic study on a large cohort of POI patients.<p class=...

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...