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

Yasuhiko Kamada, Y Kamada, Kamada Y, Nakatsuka M, Mikiya Nakatsuka, M Nakatsuka, Kazuo Asagiri, K Asagiri, Asagiri K, Soichi Noguchi, Noguchi S, S Noguchi, Habara T, T Habara, Toshihiro Habara, Masayo Takata, M Takata, Takata M, T Kudo, Takafumi Kudo, Kudo T
Human Reproduction · 2000 · vol. 15(12) , pp. 2512–2519 · doi:10.1093/humrep/15.12.2512 · PMID:11098019 · W2102107840
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This study found that GnRH agonists suppressed nitric oxide synthases and peroxynitrite generation in adenomyosis, potentially explaining therapeutic and adverse effects of this treatment.

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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.

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Condition tags

endometriosisadenomyosis

MeSH descriptors

Endometriosis Gonadotropin-Releasing Hormone Nitrates Nitric Oxide Synthase Tyrosine Adult Adult Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium Epithelial Cells Epithelial Cells Epithelial Cells Female Female Follicular Phase Follicular Phase

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (33)

Cited by (25)

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