This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mizutani, T. Articles by Terada, N. Search for Related Content PubMed PubMed Citation Articles by Mizutani, T. Articles by Terada, N.

Suppression of Cell Proliferation and Induction of Apoptosis in Uterine Leiomyoma by Gonadotropin-Releasing Hormone Agonist (Leuprolide Acetate)

Department of Obstetrics and Gynecology (T.M., K.N.), Osaka Prefectural Hospital, Sumiyoshi, Osaka 588 Japan; and Department of Pathology (A.S., N.T.), Hyogo College of Medicine, Hyogo 663 Japan

Abstract

Cell proliferation and apoptosis in uterine leiomyoma were investigated during therapy with GnRH agonist (GnRHa). Patients with uterine leiomyomas were injected with 3.75 mg GnRHa (depot leuprolide acetate) at intervals of 4 weeks and underwent hysterectomy or myomectomy at the 2nd, 4th, 8th, 12th, or 16th week of GnRHa therapy. Tissue sections of leiomyomas from these patients and from control patients (control patients received no GnRHa therapy) were stained with the Ki-67 antibody or by an in situ DNA 3'-end labeling method, and numbers of Ki-67 immunostained cells and DNA 3'-end-labeled cells per cm² were examined as indices of cell proliferation and apoptosis, respectively. The number of Ki-67 immunostained cells/cm² in leiomyomas at the 2nd week of the GnRHa therapy was comparable with that of control patients. However, it decreased to a level less than one forth that of control patients at the 4th week, and it remained at similar low levels at the 8th, 12th, and 16th week. The number of DNA 3'-end-labeled cells/cm² in leiomyomas of control patients and in leiomyomas at the 2nd, 8th, 12th, and 16th weeks of GnRHa therapy were at low levels but, at the 4th week, was at an extremely high level (about 5 times more than that of control patients). The present results indicate that GnRHa therapy suppresses cell proliferation and causes a transient increase in apoptosis in uterine leiomyomas.

This article has been cited by other articles:

				C. K. Cheng and P. C. K. Leung Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans Endocr. Rev., April 1, 2005; 26(2): 283 - 306. [Abstract] [Full Text] [PDF]

				X. Luo, L. Ding, J. Xu, R. S. Williams, and N. Chegini Leiomyoma and Myometrial Gene Expression Profiles and Their Responses to Gonadotropin-Releasing Hormone Analog Therapy Endocrinology, March 1, 2005; 146(3): 1074 - 1096. [Abstract] [Full Text] [PDF]

				T. Maruo, N. Ohara, J. Wang, and H. Matsuo Sex steroidal regulation of uterine leiomyoma growth and apoptosis Hum. Reprod. Update, May 1, 2004; 10(3): 207 - 220. [Abstract] [Full Text] [PDF]

				G. Bifulco, C. Miele, M. Pellicano, A. Trencia, M. Ferraioli, F. Paturzo, G.A. Tommaselli, F. Beguinot, and C. Nappi Molecular mechanisms involved in GnRH analogue-related apoptosis for uterine leiomyomas Mol. Hum. Reprod., January 1, 2004; 10(1): 43 - 48. [Abstract] [Full Text] [PDF]

				S.-C. Huang, M.-J. Tang, Y.-M. Cheng, K.-F. Hsu, C.-L. Ho, and C.-Y. Chou Enhanced Polyadenosine Diphosphate-Ribosylation in Gonadotropin-Releasing Hormone Agonist-Treated Uterine Leiomyoma J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 5009 - 5016. [Abstract] [Full Text] [PDF]

				N. Chegini, J. Verala, X. Luo, J. Xu, and R. S. Williams Gene Expression Profile of Leiomyoma and Myometrium and the Effect of Gonadotropin Releasing Hormone Analogue Therapy Reproductive Sciences, April 1, 2003; 10(3): 161 - 171. [Abstract] [PDF]

				N. Chegini and L. Kornberg Gonadotropin Releasing Hormone Analogue Therapy Alters Signal Transduction Pathways Involving Mitogen-Activated Protein and Focal Adhesion Kinases in Leiomyoma Reproductive Sciences, January 1, 2003; 10(1): 21 - 26. [Abstract] [PDF]

				N. Chegini, C. Ma, X.M. Tang, and R.S. Williams Effects of GnRH analogues, `add-back' steroid therapy, antiestrogen and antiprogestins on leiomyoma and myometrial smooth muscle cell growth and transforming growth factor-{beta} expression Mol. Hum. Reprod., December 1, 2002; 8(12): 1071 - 1078. [Abstract] [Full Text] [PDF]

				S.-C. Huang, M.-J. Tang, K.-F. Hsu, Y.-M. Cheng, and C.-Y. Chou Fas and Its Ligand, Caspases, and Bcl-2 Expression in Gonadotropin-Releasing Hormone Agonist-Treated Uterine Leiomyoma J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4580 - 4586. [Abstract] [Full Text] [PDF]