Growth hormone induces eNOS expression and nitric oxide release in a cultured human endothelial cell line.
Growth hormone deficiency is linked to cardiovascular disease and particularly increased peripheral vascular resistance. Surprisingly, its role in endothelial nitric oxide (NO) synthetase (eNOS) regulation and NO release is basically unknown. We therefore studied the effects of different doses of somatotropin in cultures of a human endothelial cell line (EAhy926). We investigated expression and activity of eNOS, as well as other target genes known to be deregulated in cardiovascular disease including E-selectin and the lectin-like oxidized low density lipoprotein receptor. Treatment of cultured human endothelial cells with somatotropin resulted in significant (P<0.05) increases of eNOS gene and protein expression, as well as NO release, whereas production of intracellular reactive oxygen species was significantly reduced, at the highest somatotropin dose level. The enhanced eNOS gene/protein expression and enzyme activity correlate well. Our findings are suggestive for a novel role of growth hormone in endothelial biology, and particularly NO production.
Thum
Thomas
T
Fraunhofer Institute of Toxicology and Experimental Medicine (ITEM), Drug Research and Medical Biotechnology, 30625, Hannover, Germany.
Tsikas
Dimitris
D
Frölich
Jürgen C
JC
Borlak
Jürgen
J
D015153:Blotting, Western; D002460:Cell Line; D021983:Cyclophilins / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D019040:E-Selectin / Q000096:biosynthesis; D004727:Endothelium / Q000166:cytology* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D011973:Receptors, LDL / Q000096:biosynthesis; D051131:Receptors, Oxidized LDL; D017481:Receptors, Somatostatin / Q000096:biosynthesis; D051127:Scavenger Receptors, Class E
D017931:DNA Primers; D019040:E-Selectin; C495137:OLR1 protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D017481:Receptors, Somatostatin; D051127:Scavenger Receptors, Class E; D009569:Nitric Oxide; D013006:Growth Hormone; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D017526:Receptor, IGF Type 1; D021983:Cyclophilins