GnRH agonist decreases endothelial nitric oxide synthase (eNOS) expression in leiomyoma.
OBJECTIVES To define the effect of GnRH agonist (GnRHa) treatment on endothelial nitric oxide synthase (eNOS) expression in leiomyoma. As eNOS expression is more pronounced in leiomyoma compared to parental myometrium, we hypothesized that the mechanism(s) of tumor shrinkage by GnRHa may be due to decreased nitric oxide (NO) production in leiomyoma.


METHODS
Eleven patients with leiomyoma were operated for myoma enucleation by laparatomy. Six of them were treated with GnRHa every 28 days, three times before the operation. The remaining five patients who had no treatment prior to operation formed the control group. Blood was drawn from the patients before treatment and on the day of operation for the assay of serum estradiol (E(2)). Immunohistochemical localization of eNOS expression in leiomyoma and myometrium in treated patients, and in leiomyoma in the control group, was performed using monoclonal antibodies specific to eNOS.


RESULTS
All treated subjects showed a significant reduction of fibroid volume at the end of therapy. eNOS-positive cells were localized primarily within the vascular endothelium and smooth muscle cells, but had weak expression in fibroid and myometrial muscle cells in the treated group. The immunoreactivity was similar for both the leiomyoma and myometrium (P > 0.05). In contrast to this, the control group had shown strong expression in leiomyoma muscle cells (P < 0.005) in addition to the vascular endothelium and smooth muscle cells.


CONCLUSIONS
GnRHa-induced tumor shrinkage should be due to diminished eNOS expression, most probably by lowering estrogen secretion.
Gokdeniz
R
R
Department of Obstetrics and Gynecology, Inonu University, Malatya, Turkey. gokdeniz@superonline.com
Ozen
S
S
Mizrak
B
B
Bazoglu
N
N
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III