{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T15:15:53Z","timestamp":1760886953650},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,5,14]],"date-time":"2002-05-14T00:00:00Z","timestamp":1021334400000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2002,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>objectives<\/jats:bold> \u2002Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro\u2010atherogenic state associated with adult GHD.<\/jats:p><jats:p><jats:bold>design and patients<\/jats:bold> In a randomized, double\u2010blind, placebo\u2010controlled study we investigated the effects of GH replacement on low\u2010density lipoprotein (LDL) oxidation and neutrophil superoxide (O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>) generating capacity in 32 GHD adults (19 males, 13 females; age range 19\u201364\u00a0years) over 3\u00a0months. Thirty age\u2010 and sex\u2010matched healthy controls were also studied.<\/jats:p><jats:p><jats:bold>measurements<\/jats:bold> Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper\u2010catalysed lag phase of LDL oxidation. Neutrophil O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>generating capacity was assessed by a lucigenin\u2010based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis.<\/jats:p><jats:p><jats:bold>results<\/jats:bold> Compared to controls, GHD subjects had higher LDL cholesterol (4\u00b70\u00a0\u00b1\u00a00\u00b78 <jats:italic>vs.<\/jats:italic> 3\u00b75\u00a0\u00b1\u00a00\u00b79\u00a0mmol\/l, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b701) and higher triglyceride concentrations (2\u00b73\u00a0\u00b1 1\u00b75 <jats:italic>vs.<\/jats:italic> 1\u00b71\u00a0\u00b1\u00a00\u00b77\u00a0mmol\/l, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001) but lower HDL cholesterol (1\u00b71\u00a0\u00b1\u00a00\u00b73\u00a0mmol\/l <jats:italic>vs.<\/jats:italic> 1\u00b74\u00a0\u00b1\u00a00\u00b74\u00a0mmol\/l, <jats:italic>P<\/jats:italic>\u00a0&lt; 0\u00b701), lower levels of HPOs (0\u00b772\u00a0\u00b1\u00a00\u00b735 <jats:italic>vs.<\/jats:italic> 0\u00b792\u00a0\u00b1 0\u00b720\u00a0\u00b5<jats:sc>m<\/jats:sc>, P\u00a0&lt;\u00a00\u00b701) and lower basal (2\u00b75\u00a0\u00b1\u00a01\u00b75 <jats:italic>vs.<\/jats:italic> 4\u00b75\u00a0\u00b1\u00a02\u00b73\u00a0mV\/5\u00a0\u00d7\u00a010<jats:sup>5<\/jats:sup> neutrophils, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b701) and peak post\u2010activation levels (23\u00b72\u00a0\u00b1\u00a011\u00b71 <jats:italic>vs.<\/jats:italic> 34\u00b74\u00a0\u00b1\u00a015\u00b76\u00a0mV\/5\u00a0\u00d7\u00a010<jats:sup>5<\/jats:sup> neutrophils, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b701) of neutrophil O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> generation. GH replacement resulted in an increase in HPOs from 0\u00b770\u00a0\u00b1\u00a00\u00b739 to 0\u00b786\u00a0\u00b1\u00a00\u00b719\u00a0\u00b5<jats:sc>m<\/jats:sc> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b705), although there was no change in the lag time of LDL oxidation. Neutrophil O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> generating capacity was enhanced with a rise in basal O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> generation from 2\u00b78\u00a0\u00b1\u00a01\u00b74 to 5\u00b74\u00a0\u00b1\u00a04\u00b76\u00a0mV\/5\u00a0\u00d7\u00a010<jats:sup>5<\/jats:sup> neutrophils (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b705) and in peak post\u2010activation O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> generation from 21\u00b79\u00a0\u00b1\u00a09\u00b75 to 35\u00b78\u00a0\u00b1\u00a021\u00b77\u00a0mV\/5\u00a0\u00d7\u00a010<jats:sup>5<\/jats:sup> neutrophils (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b705). LDL cholesterol was reduced from 4\u00b71\u00a0\u00b1\u00a00\u00b78\u00a0mmol\/l to 3\u00b75\u00a0\u00b1\u00a00\u00b78\u00a0mmol\/l (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b701). No significant changes in measured parameters occurred in the placebo group.<\/jats:p><jats:p><jats:bold>conclusions<\/jats:bold> Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro\u2010atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte\u2013lipoprotein interactions.<\/jats:p>","DOI":"10.1046\/j.1365-2265.2002.01493.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T10:53:08Z","timestamp":1047379988000},"page":"449-455","source":"Crossref","is-referenced-by-count":16,"title":["Effects of GH on lipid peroxidation and neutrophil superoxide anion\u2010generating capacity in hypopituitary adults with GH deficiency"],"prefix":"10.1111","volume":"56","author":[{"given":"J. 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