Epithelial sodium channel is a key mediator of growth hormone-induced sodium retention in acromegaly. - Archive ouverte HAL Access content directly
Journal Articles Endocrinology Year : 2008

Epithelial sodium channel is a key mediator of growth hormone-induced sodium retention in acromegaly.

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Abstract

Acromegalic patients present with volume expansion and arterial hypertension, but the renal sites and molecular mechanisms of direct antinatriuretic action of GH remain unclear. Here, we show that acromegalic GC rats, which are chronically exposed to very high levels of GH, exhibited a decrease of furosemide-induced natriuresis and an increase of amiloride-stimulated natriuresis compared with controls. Enhanced Na(+),K(+)-ATPase activity and altered proteolytic maturation of epithelial sodium channel (ENaC) subunits in the cortical collecting ducts (CCDs) of GC rats provided additional evidence for an increased sodium reabsorption in the late distal nephron under chronic GH excess. In vitro experiments on KC3AC1 cells, a murine CCD cell model, revealed the expression of functional GH receptors and IGF-I receptors coupled to activation of Janus kinase 2/signal transducer and activator of transcription 5, ERK, and AKT signaling pathways. That GH directly controls sodium reabsorption in CCD cells is supported by: 1) stimulation of transepithelial sodium transport inhibited by GH receptor antagonist pegvisomant; 2) induction of alpha-ENaC mRNA expression; and 3) identification of signal transducer and activator of transcription 5 binding to a response element located in the alpha-ENaC promoter, indicative of the transcriptional regulation of alpha-ENaC by GH. Our findings provide the first evidence that GH, in concert with IGF-I, stimulates ENaC-mediated sodium transport in the late distal nephron, accounting for the pathogenesis of sodium retention in acromegaly.
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Dates and versions

inserm-00266634 , version 1 (08-04-2008)

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Peter Kamenicky, Say Viengchareun, Anne Blanchard, Geri Meduri, Philippe Zizzari, et al.. Epithelial sodium channel is a key mediator of growth hormone-induced sodium retention in acromegaly.: Antinatriuretic action of growth hormone. Endocrinology, 2008, 149 (7), pp.3294-305. ⟨10.1210/en.2008-0143⟩. ⟨inserm-00266634⟩
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