Validation of Rat Endometriosis Model by Using Raloxifene as a Positive Control for the Evaluation of Novel SERM Compounds

Z Yao, Zuliang Yao, Yao Z, Shen X, Xun Shen, X Shen, Capodanno I, I Capodanno, Isabella Capodanno, Donnelly M, M Donnelly, Marcie J. Donnelly, Fenyk-Melody J, J Fenyk-Melody, Judy Fenyk‐Melody, Hausamann J, J Hausamann, Christian Nunes da Silva, Nunes C, C. Nunes, J Strauss, John R. Strauss, Strauss J, Vakerich K, K Vakerich, Ken Vakerich
Journal of investigative surgery : the official journal of the Academy of Surgical Research · 2005 · vol. 18(4) , pp. 177–183 · doi:10.1080/08941930591004412 · PMID:16126628 · W1965260226
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This study validated a rat endometriosis model by establishing that raloxifene at 10.0 mg/kg effectively reduced endometriotic implants, making it a reliable positive control for testing new SERM compounds.

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Abstract

Approximately 10% of women of reproductive age suffer from endometriosis, a potentially painful disease process and important cause of female infertility. Raloxifene, a commercially available SERM (selective estrogen receptor modulator) compound, used for the treatment of postmenopausal osteoporosis, has preclinically demonstrated its estrogen antagonist effect on uterine tissue in rats. There is potential that SERM compounds may become a viable treatment option for human endometriosis, although more investigation is needed. In this study, raloxifene was administered at various doses to determine the efficacy and an appropriate dose level for use as a positive control in a rat model of endometriosis. Prior to dose administration, all rats underwent a bilateral ovariectomy, autologous transplantation of uterine tissue onto the peritoneal surface of the abdominal wall, and implantation of a subcutaneous estrogen pellet (E2). Two separate postsurgical experiments were performed. In experiment 1, following a 4-wk recovery, the rats bearing implants were assigned to three groups: (1) removal of the E2 pellet and dosing vehicle only (n = 7); (2) E2 and vehicle (n = 6); and (3) E2 and raloxifene at 10.0 mg/kg (n = 6). In experiment 2, also following a 4-week recovery, the rats bearing implants were assigned to five groups (n = 8/group): (1) E2 and vehicle only; (2) E2 and raloxifene, 0.3 mg/kg/d; (3) E2 and raloxifene, 1.0 mg/kg/d; (4) E2 and raloxifene, 3.0 mg/kg/d; (5) E2 and raloxifene, 10.0 mg/kg/d. All rats were dosed orally BID for 14 d. At the end of the study, the implanted endometrium was remeasured and compared to the pretreatment measurement. The results from both studies demonstrated that Raloxifene at only one dose (10.0 mg/kg) displayed significant implant regression (p < .05). Subsequently, our rat endometriosis experimental model consistently uses the exogenous E2 pellet and raloxifene at 10 mg/kg, BID, as a positive control to help screen and compare novel SERM compounds.

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Condition tags

endometriosisinfertility

MeSH descriptors

Disease Models, Animal Endometriosis Raloxifene Hydrochloride Rats, Sprague-Dawley Selective Estrogen Receptor Modulators Animals Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Organ Size Raloxifene Hydrochloride Rats Selective Estrogen Receptor Modulators

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References (9)

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