title: Exposure to ethanol induces oxidative damage in the pituitary gland.
abstract: Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone and decreased or inappropriately normal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels suggesting a functional defect in the pituitary. The molecular mechanisms behind this disorder are undefined. A role for ethanol-induced oxidative damage in the pathophysiology is supported by studies in liver, muscle, and heart of experimental animals, but there is limited evidence in the pituitary. We examined markers of oxidative damage to lipids and proteins in pituitaries from rats consuming ethanol for 5, 10, 20, 30, and 60 days in addition to markers of damage to nucleic acids in pituitaries after 60 days of ethanol exposure. There were increases in 8-oxo-deoxyguanosine immunoreactivity, a marker of oxidative damage to nucleic acids, and an overall increase in malondialdehyde and 4-hydroxynonenal, markers of lipid peroxidation. Protein carbonylation and protein nitrotyrosination, markers of protein oxidation, were significantly increased after 30 days and 60 days of ethanol consumption, respectively. After 60 days of ethanol exposure, TUNEL assay revealed that cell death in the ethanol-treated pituitaries was not significantly different from that in the pair-fed controls at the time of examination. We also measured serum testosterone, FSH, and LH after ethanol consumption for 5, 10, 20, 30, and 60 days. Through 5 to 60 days of ethanol exposure, testosterone levels were consistently lower whereas LH and FSH were inappropriately unchanged, suggesting pituitary malfunction. These results provide evidence for ethanol-induced oxidative damage at the pituitary level, which may contribute to pituitary dysfunction.
authors.affiliation: The Neuroscience Program, Loyola University Medical Center, Maywood, IL 60153, USA.
authors.forename: Jian-Ching
authors.initials: JC
authors.lastname: Ren
authors.forename: Ali
authors.initials: A
authors.lastname: Banan
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
authors.forename: Qianlong
authors.initials: Q
authors.lastname: Zhu
authors.forename: Nancy
authors.initials: N
authors.lastname: Lapaglia
authors.forename: John
authors.initials: J
authors.lastname: McNulty
authors.forename: Nicholas V
authors.initials: NV
authors.lastname: Emanuele
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Emanuele
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D004140:Dinitrophenols / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005640:Follicle Stimulating Hormone / Q000097:blood; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009696:Nucleic Acids / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010902:Pituitary Gland / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000009:adverse effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000447:Aldehydes; D002492:Central Nervous System Depressants; D004140:Dinitrophenols; D009696:Nucleic Acids; D009705:Nucleosides; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D000431:Ethanol; D013739:Testosterone; D014443:Tyrosine; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C027576:4-hydroxy-2-nonenal