[Influences of gonadotropin releasing hormone agonist treatment on nitric oxide synthase expression in women with endometriosis and infertility].
OBJECTIVE
To explore the expression of endothelial and inducible nitric oxide synthase (eNOS and iNOS) in the eutopic endometria of patients with endometriosis and infertility, and to detect the effect of gonadotropin releasing hormone agonist (GnRH-a) therapy on their expressions.


METHODS
Immunohistochemistry and Western immunoblot assay were used to screen eNOS and iNOS expression in endometria of patients with stage III to IV endometriosis and infertility without (30 cases, endometriosis group) and with GnRH-a treatment (18 cases, treatment group), and of 19 patients with carcinoma in situ of the cervix (control group). Using electrochemiluminescence immunoassay, serum estradiol (E(2)) or progesterone (P) concentrations were assayed.


RESULTS
eNOS was localized predominantly to the endometrial glandular epithelium, luminal epithelium, and microvascular endothelium. iNOS staining was light, and it, when present, was predominantly found in glandular epithelium and stromal cells. By Western immunoblot analysis, iNOS was not detected. During the early-, mid-, and late-proliferative phases, and the early-, mid-, and late-secretory phases, endometrial eNOS protein relative levels were 0.30 +/- 0.04, 0.40 +/- 0.03, 0.49 +/- 0.03, 0.43 +/- 0.04, 0.55 +/- 0.04 and 0.48 +/- 0.03 in endometriosis group, 0.22 +/- 0.03, 0.37 +/- 0.03, 0.45 +/- 0.04, 0.35 +/- 0.05, 0.50 +/- 0.03 and 0.41 +/- 0.00 in treatment group, and 0.21 +/- 0.03, 0.33 +/- 0.03, 0.45 +/- 0.04, 0.40 +/- 0.03, 0.47 +/- 0.05 and 0.41 +/- 0.03 in control group, respectively. Eutopic endometria in endometriosis group showed higher levels of eNOS protein than that of the control group, but a significant difference was found only in early-, mid-proliferative phases and mid-, late-secretory phases (P < 0.05). Compared with endometriosis group, endometrial eNOS levels in treatment group were reduced, but a significant difference was found only in early proliferative phase and early-, mid-secretory phases (P < 0.05). A significant positive correlation was found between serum E(2) or P concentrations and endometrial expression of eNOS (P < 0.01).


CONCLUSIONS
The higher endometrial expression of eNOS in patients with stage III to IV endometriosis may be related to the pathogenesis of endometriosis and the associated subfertility. The expression of eNOS is markedly reduced by administration of GnRH-a.
Wang
Jian-hua
JH
Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
Zhou
Fu-zhen
FZ
Dong
Min-yue
MY
Yuan
Li
L
D000328:Adult; D004715:Endometriosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000627:therapeutic use; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D007987:Gonadotropin-Releasing Hormone; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III