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This Article Full Text Full Text (PDF) All Versions of this Article: 292/2/F723    most recent 00276.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Dimke, H. Articles by Frische, S. Search for Related Content PubMed PubMed Citation Articles by Dimke, H. Articles by Frische, S.

Acute growth hormone administration induces antidiuretic and antinatriuretic effects and increases phosphorylation of NKCC2

¹The Water and Salt Research Centre, Institute of Anatomy, University of Aarhus, Aarhus; ²Medical Department M and Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Aarhus; ⁴Centre for Basic Psychiatric Research, Aarhus University Hospital; ⁵The Water and Salt Research Centre, Clinical Institute, University of Aarhus, Aarhus, Denmark; and ³Institut National de la Santé et de la Recherche Médicale U652, IFR58, Institut des Cordeliers, Université René Descartes and Université Pierre et Marie Curie, Paris, France

Submitted 19 July 2006 ; accepted in final form 16 October 2006

Growth hormone (GH) has antidiuretic and antinatriuretic effects in rats and humans, but the molecular mechanisms responsible for these effects are unknown. The aim of this study was to investigate the mechanisms behind the acute renal effects of GH in rats. Female rats received rat (r)GH (2.8 mg/kg sc) or saline and were placed in metabolic cages for 5 h. Urinary excretion of electrolytes and urinary volume were reduced after rGH injection, while urine osmolality was increased. Creatinine and lithium clearance remained unchanged, suggesting that rGH increases reabsorption in segments distal to the proximal tubule. Total plasma insulin-like growth factor I (IGF-I) levels did not change, while cortical IGF-I mRNA abundance was increased. The relative abundance of total and Ser²⁵⁶-phosphorylated aquaporin 2 was found to be unchanged by immunoblotting, whereas a significant increase of Thr⁹⁶ and Thr¹⁰¹-phosphorylated NKCC2 (renal Na⁺, K⁺, 2Cl^– cotransporter) was found in the inner stripe of outer medulla thick ascending limbs (mTAL). Additionally, an increased NKCC2 expression was observed in the cortical region. Immunohistochemistry confirmed these findings. The density of NKCC2 molecules in the apical membrane of mTAL cells appeared to be unchanged after rGH injection evaluated by immunoelectron microscopy. Basolateral addition of rGH or IGF-I to microperfused rat mTAL segments did not change transepithelial voltage. In conclusion, GH appears to exert its acute antinatriuretic and antidiuretic effects through indirect activation of NKCC2 in the mTAL.

thick ascending limb; sodium; insulin-like growth factor I; GH; kidney