Uterine leiomyomas, also called fi broids, are the most common reproductive tract neoplasm and the leading indication for hysterectomy in premenopausal women. The discovery and development of medicinal therapies for uterine leiomyoma have been hampered by a lack of understanding regarding the etiology and molecular mechanisms underlying the development of these lesions. Although the estrogen responsiveness of uterine leiomyoma is well established, the impact of environmental estrogens and their contribution to the development of these tumors is currently unknown. The Eker rat model of uterine leiomyoma has proven useful for addressing these issues and understanding the pathophysiology of this disease. The Eker rat is the only animal model that develops spontaneous uterine leiomyomas, and these tumors share many characteristics with those found in humans. The availability of tumor-derived cell lines from these rats has made this a valuable in vitro/in vivo model system for experimental studies to investigate molecular mechanisms of disease and to design interventional and preventative strategies for this clinically relevant tumor.
Andreyko JL, Marshall LA, Dumesic DA, Jaffe RB (1987). Therapeutic uses of gonadotropin-releasing hormone analogs. Obstet Gynecol Surv42: 1—21.
4.
Burroughs KD , Howe SR, Okubo Y., Fuchs-Young R., LeRoith D., Walker CL (in press). Disregulation of insulin-like growth factor-I signalling in uterine leiomyoma. Mol Carcinog .
5.
Burroughs K. , Fuchs-Young R., Davis B., Walker C. (2000). Altered hormonal responsiveness of proliferation and apoptosis during myometrial maturation and the development of uterine leiomyomas. Biol Reprod63: 1322—1330.
6.
Burroughs KD , Kiguchi K., Howe SR, Fuchsyoung R., Trono D., Barrett JC, Walker C. (1997). Regulation of apoptosis in uterine leiomyomata. Endocrinology138: 3056—3064.
Chiaffarino F. , Parazzini F., La Vecchia C., Chatenoud L., Di Cintio E., Marsico S. (1999). Diet and uterine myomas. Obstet Gynecol94: 395—398.
9.
Chiaffarino F. , Parazzini F., La Vecchia C., Marsico S., Surace M., Ricci E. (1999). Use of oral contraceptives and uterine fibroids: Results from a case-control study. Br J Obstet Gynaecol106: 857 — 860.
10.
Chiaffarino F. , Parazzini F., La Vecchia C., Ricci E., Crosignani PG (1998). Oral contraceptive use and benign gynecologic conditions. A review . Contraception57: 11—18.
11.
Cramer S., Patel A. (1990). The frequency of uterine leiomyomas. Am J Clin Pathol94: 435—438.
12.
Everitt JI, Wolf DC, Howe SR, Goldsworthy TL, Walker C. (1995). Rodent model of reproductive tract leiomyomata. Clinical and pathological features. Am J Pathol146: 1556—1567.
13.
Fuchs-Young R. , Howe S., Hale L., Miles R., Walker C. (1996). Inhibition of estrogen-stimulated growth of uterine leiomyomas by selective estrogen receptor modulators. Mol Carcinog17: 151—159.
14.
Ghahary A., Chakrabarti S., Murphy LJ (1990). Localization of the sites of synthesis and action of insulin-like growth factor-I in the rat uterus. Mol Endocrinol4: 191—195.
15.
Grese TA, Dodge JA (1998). Selective estrogen receptor modulators (SERMs) . Curr Pharm Design4: 71—92.
16.
Hodges LC, Bergerson JS, Hunter DS, Walker CL (2000). Estrogenic effects of organochlorine pesticides on uterine leiomyoma cells in vitro. Toxicol Sci54: 355—364.
17.
Howe SR, Everitt JL, Gottardis MM, Walker C. (1997). Rodent model of reproductive tract leiomyomata: Characterization and use in preclinical therapeutic studies. Prog Clin Biol Res396: 205— 215.
18.
Howe SR, Gottardis MM, Everitt JI, Goldsworthy TL, Wolf DC, Walker C. (1995). Rodent model of reproductive tract leiomyomata. Establishment and characterization of tumor-derived cell lines. Am J Pathol146: 1568—1579.
19.
Howe SR, Gottardis MM, Everitt JI, Walker C. (1995). Estrogen stimulation and tamoxifen inhibition of leiomyoma cell growth in vitro and in vivo. Endocrinology136: 4996—5003.
20.
Hoyer AP, Grandjean P., Jorgensen T., Brock JW, Hartvig HB (1998). Organochlorine exposure and risk of breast cancer . Lancet352: 1816—1820.
21.
Hunter DS, Hodges LC, Vonier PM, Fuchs-Young R., Gottardis MM, Walker CL (1999). Estrogen receptor activation via activation function 2 predicts agonism of xenoestrogens in normal and neoplastic cells of the uterine myometrium. Cancer Res59: 3090 — 3099.
22.
Kjerulff KH , Langenberg P., Seidman JD, Stolley PD, Guzinski GM (1996). Uterine leiomyomas. Racial differences in severity, symptoms and age at diagnosis . J Reprod Med41: 483—490.
23.
Marshall LM , Spiegelman D., Barbieri RL, Goldman MB, Manson JE, Colditz GA, Willett WC, Hunter DJ (1997). Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol90: 967—973.
24.
Marshall LM , Spiegelman D., Goldman MB, Manson JE, Colditz GA, Barbieri RL, Stampfer MJ, Hunter DJ (1998). A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata. Fertil Steril70: 432—439.
25.
Marshall LM , Spiegelman D., Manson JE, Goldman MB, Barbieri RL, Stampfer MJ, Willett WC, Hunter DJ (1998). Risk of uterine leiomyomata among premenopausal women in relation to body size and cigarette smoking. Epidemiology9: 511—517.
26.
Murkies AL, Wilcox G., Davis SR (1998). Clinical review 92: Phytoestrogens. J Clin Endocrinol Metab83: 297—303.
27.
Murphy LJ, Ghahary A. (1990). Uterine insulin-like growth factor-1: Regulation of expression and its role in estrogen-induced uterine proliferation. Endocr Rev11: 443—453.
28.
Murphy LJ, Murphy LC, Friesen HG (1987). Estrogen induces insulin-like growth factor-I expression in the rat uterus. Mol Endocrinol1: 445—450.
29.
Parazzini F. , Negri E., La Vecchia C., Chatenoud L., Ricci E., Guarnerio P. (1996). Reproductive factors and risk of uterine fi broids. Epidemiology7: 440—442.
30.
Parazzini F. , Negri E., La Vecchia C., Fedele L., Rabaiotti M., Luchini L. (1992). Oral contraceptive use and risk of uterine fibroids. Obstet Gynecol79: 430 — 433.
31.
Parazzini F. , Negri E., La Vecchia C., Rabaiotti M., Luchini L., Villa A., Fedele L. (1996). Uterine myomas and smoking. Results from an Italian study. J Reprod Med41: 316—320.
32.
Rao GN (1996). Influence of diet on tumors of hormonal tissues . In: Cellular and Molecular Mechanisms of Hormonal Carcinogenesis , Huff J, Boyd J, Barrett JC (eds). Wiley-Liss, New York, pp 41—56.
33.
Richards RG , DiAugustine RP, Petrusz P., Clark GC, Sebastian J. (1996). Estradiol stimulates tyrosine phosphorylation of the insulin-like growth factor-1 receptor and insulin receptor substrate-1 in the uterus. Proc Natl Acad Sci USA93: 12002—12007.
34.
Rivlin ME, Patel RB, Hess LW, Hess DB, Meeks GR (1994). Leuprolide acetate depot for the treatment of uterine leiomyomas. Changes in bone density, uterine volume and uterine vascular resistive index. J Reprod Med39: 663—666.
35.
Walker C., Burroughs K., Davis B., Sowell K., Everitt J., Fuchs-Young R. (2000). Preclinical evidence for therapeutic effi cacy of selective estrogen receptor modulators for uterine leiomyoma. J Soc Gynecol Invest7: 249—256.
36.
Washburn S. , Burke GL, Morgan T., Anthony M. (1999). Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause6: 7—13.
37.
Werner H., Le Roth D. (1997). The insulin-like growth factor-I receptor signaling pathways are important for tumorigenesis and inhibition of apoptosis. Crit Rev Oncog8: 71—92.
38.
Wolff MS, Toniolo PG, Lee EW, Rivera M., Dubin N. (1993). Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst85: 648—652.
