GnRH agonist-suppressed expression of nitric oxide synthases and generation of peroxynitrite in adenomyosis.
Because overproduction of nitric oxide (NO) and peroxynitrite is known to cause tissue injury, the expression of NO synthases (NOS) and generation of peroxynitrite were investigated in adenomyosis. Immunoreactivities to endothelial and inducible NOS demonstrated phase-dependent changes in normal endometrium, and in eutopic endometrium of adenomyosis. However, NOS were expressed throughout the menstrual cycle in ectopic endometrium from the majority of patients with adenomyosis. Nitrotyrosine, a footprint of peroxynitrite, was detected concomitantly with NOS protein. This suggested that high doses of NO and superoxide are produced in the ectopic endometrium, presumably by stimulation with bioactive molecules such as cytokines and growth factors. The expression of NOS and generation of peroxynitrite were markedly reduced by administration of gonadotrophin-releasing hormone agonists (GnRHa). The suppression of serum concentrations of nitrite/nitrate, stable metabolites of NO, by long-term administration of GnRHa was also demonstrated. The suppression of synthesis of NO and/or peroxynitrite may be part of both the therapeutic and adverse effects of GnRHa therapy.
Kamada
Y
Y
Department of Obstetrics and Gynecology, Okayama University Medical School, Okayama-city, Okayama, Japan.
Nakatsuka
M
M
Asagiri
K
K
Noguchi
S
S
Habara
T
T
Takata
M
M
Kudo
T
T
D000328:Adult; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000737:chemistry / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D005498:Follicular Phase; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008183:Luteal Phase; D009566:Nitrates / Q000097:blood / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D017154:Stromal Cells / Q000201:enzymology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D009566:Nitrates; D009573:Nitrites; C039642:peroxynitric acid; D009569:Nitric Oxide; D007987:Gonadotropin-Releasing Hormone; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III