GnRH agonist-suppressed expression of nitric oxide synthases and generation of peroxynitrite in adenomyosis

Yasuhiko Kamada, Mikiya Nakatsuka, Kazuo Asagiri, Soichi Noguchi, Toshihiro Habara, Masayo Takata, Takafumi Kudo

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Abstract

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.

Original languageEnglish
Pages (from-to)2512-2519
Number of pages8
JournalHuman Reproduction
Volume15
Issue number12
DOIs
Publication statusPublished - Jan 1 2000

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Keywords

  • Adenomyosis
  • GnRH agonist
  • Nitric oxide
  • Peroxynitrite

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology

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