Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to elucidate potential sites of direct GH action on the kidney, we used in situ hybridization to localize GH receptor (GHR) gene expression during the course of development and in the adult rat. In order to illuminate potential interactions between GH and insulin-like growth factor-I (IGF-I) in regulating renal function, we compared the anatomical localization of GHR messenger RNA (mRNA) with that for the IGF-I receptor and for IGF-I in the rat kidney. Low levels of GHR mRNA were present in the kidney from before birth and increased in abundance until postnatal day 40. Hypophysectomy resulted in a decrease and GH treatment resulted in an increase in renal GHR mRNA levels. Renal GHR mRNA was most abundant in the proximal straight tubule, with lesser levels present in the medullary thick ascending limb (MTAL), and it was not detected in the glomerulus or inner medulla. In contrast, IGF-I receptor mRNA was concentrated in the glomerulus, distal nephron and collecting system. The only point of convergence for GHR and IGF-I receptor mRNAs was in the MTAL, where IGF-I mRNA was localized. This segregation of GHR and IGF-I receptor gene expression in the kidney suggests that each hormone has distinct spheres of action along the nephron, with GH acting directly on the proximal straight tubule, whereas IGF-I may act on the glomerulus, distal nephron, and collecting duct. GHR expression in the MTAL, which is the site of renal IGF-I synthesis, supports the view that GH has a direct effect on renal IGF-I synthesis. Finally, it appears that in the kidney, as in other GH-sensitive tissues, GH may regulate its receptor levels.
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PMID:Renal growth hormone receptor gene expression: relationship to renal insulin-like growth factor system. 144 40

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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PMID:Epithelial sodium channel is a key mediator of growth hormone-induced sodium retention in acromegaly. 1838 93