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Enhanced Polyadenosine Diphosphate-Ribosylation in Gonadotropin-Releasing Hormone Agonist-Treated Uterine Leiomyoma

Department of Obstetrics and Gynecology (S.-C.H., Y.-M.C., K.-F.H., C.-Y.C.), Institute of Clinical Medicine (S.-C.H., M.-J.T., Y.-M.C., K.-F.H., C.-Y.C.), Department of Physiology (M.-J.T.), and Department of Pathology (C.-L.H.), College of Medicine, National Cheng Kung University, Tainan 704, Taiwan

Address all correspondence and requests for reprints to: Cheng-Yang Chou, M.D., Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan. E-mail: chougyn{at}mail.ncku.edu.tw.

This study aimed to examine the activation of poly(ADP-ribose) polymerase (PARP) and the accumulation of its end product, poly(ADP-ribose) (PAR), in uterine leiomyoma specimens obtained from 25 patients receiving Leuplin depot [leuprorelin acetate, depot (LA)] treatment and 46 control patients and explore their correlation with tumor shrinkage and degeneration caused by the therapy. Immunoblotting analysis showed that specimens from LA-treated patients had higher PARP expression. The numbers of both PARP- and PAR-immunolabeled cells were higher in leiomyoma with LA treatment. This was correlated with the clinical response of LA therapy that LA induced more leiomyoma degeneration. The analysis of power Doppler sonography indicated a progressive decrease in blood supply to tumor following LA treatment. In vitro experiments using primarily cultured leiomyoma cells exhibited that the deprivation of serum or ovarian hormones or LA directly failed to induce PARP and PAR production. Our results suggested that reduced blood flow and subsequent ischemic damages in leiomyoma could be responsible for PARP overexpression and PAR accumulation, clinical response, and tumor degeneration caused by LA treatment.

This work was supported by grants from the National Science Council, Taiwan (NSC89-2314-B-006-102, NSC90-2314-B-006-169); National Cheng Kung University Hospital (NCKUH 89-028, NCKUH 90-045); and MOE Program for Promoting Academic Excellent of Universities (91-B-FA09-1-4).

Abbreviations: 3-D, Three-dimensional; FBS, fetal bovine serum; FI, flow index; GnRH-a, GnRH agonist; LA, leuprorelin acetate; PAR, poly(ADP-ribose); PARP, PAR polymerase; ROS, reactive oxygen species; VFI, vascularization FI; VI, vascularization index.