Endocrine Abstracts

In previous work we demonstrated that various adipokines, including leptin and resistin, were expressed in the hypothalamus and anterior pituitary gland. We hypothesized that a practical approach to investigate the putative central role of such factors would be to selectively silence gene expression by RNA interference (RNAi). We tested this hypothesis using model in vitro systems : C6 glioblastoma cells , which we reported express leptin, and 3T3-L1 adipocytes which are known...

The epidemic-like increase in obesity in young people is paralleled by a rise in related diseases such as PCOS, especially in pubertal girls. Kisspeptins, encoded by the KiSS1 gene, are firmly linked with the normal control of the reproductive system and loss-of-function mutations are associated with absence of puberty. Although KiSS1 is predominantly expressed in the hypothalamus (HYP), we detected KiSS1 mRNA in rat pituitary (PIT) and adipose tissue (FAT...

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...

WNK1 and WNK4 are serine/threonine kinases, With-No-K (lysine) residue at a key catalytic position within the active site. Mutations in either cause Pseudohypoaldosteronism type II (Gordon syndrome), an autosomal dominant, hypertensive, hyperkalaemic disorder, especially responsive to thiazide diuretics (first line treatment for essential hypertension). This novel WNK pathway is implicated in normal regulation of blood pressure (BP) and distal nephron Na+/K+</s...

Regulation of the epithelial sodium channel (ENaC) trafficking in cells of the distal nephron is of major importance in the control of sodium reabsorption. Mutations in the genes compromising the molecular pathway by which corticosteroids regulate ENaC sodium reabsorption cause several hypertensive syndromes in humans. The molecular events underpinning ENaC exo- and endocytosis and the hormonal effects on ENaC trafficking are poorly understood. To start elucidating these pathw...

The foetus of a mother with previous or current Graves disease is at risk of developing thyrotoxicosis. The mother can act as a bioassay to diagnose foetal thyrotoxicosis. We describe the difficulties in managing foetal thyrotoxicosis in a mother who could not act as a bioassay because of previous Graves disease treated by total thyroidectomy.A 35year old woman fell pregnant 3 months after a total thyroidectomy for relapsed Graves disease and concomitant...

Serum gastrin (G) levels >1000 pg usually raise the suspicion for a neuroendocrine tumor (NET) secreting G. Rarely, such elevated G levels are seen in pts with pernicious anemia (PA) which most commonly is associated with autoimmune gastritis (AG) (1). AG can occur concomitantly with other autoimmune d/o incl. lymphocytic colitis (LC) (2). G stimulates enterochromaffin-like cells which increase histamine (H) secretion. H excess can cause diarrhea (D) as can bacterial overg...

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...

Renal sodium handling and responses to aldosterone (aldo) are conserved across species and intrinsic to the dominant role of the kidney in long-term blood pressure (BP) control. Molecular pathways involved in hypertensive responses to aldo and escape from these remain largely unclear despite identification of several participant genes. We have characterized renal gene expression changes in mice, receiving aldo and/or dietary salt excess, using microarray analysis and concurren...

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...