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LH Hypersecreting Mice: A Model for Ovarian Granulosa Cell Tumors

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Transgenic Models in Endocrinology

Part of the book series: Endocrine Updates ((ENDO,volume 13))

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Abstract

Proper function of the ovary requires carefully orchestrated proliferation and differentiation of granulosa cells that respond dynamically to signals from LH and FSH, and a host of other paracrine and autocrine factors. These numerous signals regulate a complex array of responsive genes. Any perturbation of these pathways, especially those that change the ratios of LH and FSH, compromises ovarian function and results in a number of outcomes including infertility, disruption of pregnancy, and even ovarian malignancy such as granulosa cell (GC) tumors.

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Reference

  1. Risma KA, Clay CM, Nett TM, Wagner T, Yun J, Nilson M. Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors. Proc Natl Mad Sci USA 1995;92:1322–1326.

    Article  CAS  Google Scholar 

  2. Keri RA, Lozada KL, Abdul-Karim FW, Nadeau JH, Nilson JR Luteinizing hormone induction of ovarian tumors: oligogenic differences between mouse strains dictates tumor disposition. Proc Natl Acad Sci USA 2000;97:383–387.

    Article  PubMed  CAS  Google Scholar 

  3. Lappohn RE, Burger HG, Bouma J, Bangah M, Krans M, de Bruijn HW. Inhibin as a marker for granulosa-cell tumors. N Engl J Med 1989;321:790–793.

    Article  PubMed  CAS  Google Scholar 

  4. Fuller PJ, Verity K, Shen Y, Mamers P, Jobling T, Burger HG. No evidence of a role for mutations or polymorphisms of the follicle-stimulating hormone receptor in ovarian granulosa cell tumors. J Clin Endocrinol Metab 1998;83;274–279.

    Article  PubMed  CAS  Google Scholar 

  5. Cooke I, O’Brien M, Chamock FM, Groome N, Ganesan TS. Inhibin as a marker for ovarian cancer. British J Cancer 1995;71:1046–1050.

    Article  CAS  Google Scholar 

  6. Amsterdam A, Selvaraj N. Control of differentiation, transformation, and apoptosis in granulosa cells by oncogenes, oncoviruses, and tumor suppressor genes. Endocr Rev 1997;18:435–461.

    Article  PubMed  CAS  Google Scholar 

  7. Bousfield GR, Perry WM, Ward DN. Gonadotropins: Chemistry and Biosynthesis. In: The Physiology of Reproduction, Second Edition (Eds: Knobil E, Neill JD), ppl749–1791. New York: Raven Press, Ltd., 1994.

    Google Scholar 

  8. Pierce J, Parsons TF. Glycoprotein hormones: structure, function. Ann Rev Biochem 1981;50:465–495.

    Article  PubMed  CAS  Google Scholar 

  9. Marshall JC, Dalkin AC, Haisenleder DJ, Paul SJ, Ortolan GA, Kelch RP. Gonadotrophin-releasing hormone pulses: Regulators of gonadotropin synthesis and ovulatory cycles. Recent Prog Horm Res 1991;47:155–189.

    PubMed  CAS  Google Scholar 

  10. Falck B. Site of production of oestrogen in rat ovary as studied in micro-transplants. Acta Physiol 1959;193:1–101.

    Google Scholar 

  11. Steinkampf MP, Mendelson CR, Simpson ER. Regulation by follicle-stimulating hormone of the synthesis of aromatase cytochrome P-450 in human granulosa cells. Mol Endocrinol 1987;1:465–471.

    Article  PubMed  CAS  Google Scholar 

  12. Haisenleder DJ, Dalkin AC, Marshall JC. Regulation of gonadotropin gene expression. In: The Physiology of Reproduction (Eds: Knobil E, Neill JD), pp1 793–1813. New York: Raven Press, Ltd., 1994.

    Google Scholar 

  13. Gharib SD, Wierman ME, Shupnik MA, Chin WW. Molecular biology of the pituitary gonadotropins. Endocr Rev 1990;11:177–199.

    Article  PubMed  CAS  Google Scholar 

  14. Balen AH, Tan SL, Jacobs HS. Hypersecretion of luteinizing hormone: a significant cause of infertility and miscarriage. Br J Obst Gyn 1993;100:1082–1089.

    Article  CAS  Google Scholar 

  15. Shoham Z, Jacobs HS, Insler V. Luteinizing hormone: its role, mechanism of action, and detrimental effects when hypersecreted during the follicular phase. Fertil Steril 1993;59:1153–1161.

    PubMed  CAS  Google Scholar 

  16. Risma KA, Hirshfield AH, Nilson JH. Elevated LH in prepubertal transgenic mice causes hyperandrogenemia, precocious puberty, and substantial ovarian pathology. Endocrinology 1997;138:3540–3547.

    Article  PubMed  CAS  Google Scholar 

  17. Richards JS. Maturation of ovarian follicles: actions and interactions of pituitary and ovarian hormones on follicular cell differentiation. Physiol Rev 1980;60:51–89.

    PubMed  CAS  Google Scholar 

  18. Richards JS, Ireland JJ, Rao MC, Bernath GA, Midgley AR, Jr., Reichert LE, Jr. Ovarian follicular development in the rat hormone receptor regulation byestradiol, follicle stimulating hormone and luteinizing hormone. Endocrinology 1976;99:1562–1570.

    Article  PubMed  CAS  Google Scholar 

  19. Sicinski P, Donaher JL, Geng Y, Parker SB, Gardner H, Park MY, Robker RL, Richards JS, McGinnis LK, Biggers JD, Emig JJ, Bronson RT, Elledge SJ, Weinberg RA. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature 1996;384:471–474.

    Article  Google Scholar 

  20. Robker RL, Richards JS. Hormone-induced proliferation and differentiation of granulosa cells: a coordinated balance of the cell cycle regulators cyclin D2 and p27Kip1. Mol Endocrinol 1998;12:924–940.

    Article  PubMed  CAS  Google Scholar 

  21. Richards JS, Hedin L, Caston L. Differentiation of rat ovarian thecal cells: evidence for functional luteinization. Endocrinology 1986;118:1660–1668.

    Article  PubMed  CAS  Google Scholar 

  22. Fero ML, Rivkin M, Tasch M, Porter P, Carow CE, Firpo E, Polyak K, Tsai LH, Broudy V, Perlmutter RM, Kaushansky K, Roberts JM. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kipl)-deficient mice. Cell 1996;85:733–744.

    Article  PubMed  CAS  Google Scholar 

  23. Hamemik DL, Ken RA, Clay CM, Clay JN, Sherman GB, Sawyer Jr. HR, Nett TM, Nilson JH. Gonadotrope-and thyrotrope-specific expression of the human and bovine glycoprotein hormone alpha-subunit genes is regulated by distinct cis-acting elements. Mol Endocrinol 1992;6:1745–1755.

    Article  Google Scholar 

  24. Kendall SK, Saunders TL, Jin L, Lloyd RV, Glode LM, Nett TM, Ken RA, Nilson JH, Camper SA. Targeted ablation of pituitary gonadotropes in transgenic mice. Mol Endocrinol 1991;5:2025–2036.

    Article  PubMed  CAS  Google Scholar 

  25. Nilson JH, Bokar JA, Clay CM, Farmerle TA, Fenstermaker RA, Hamernik DL, Keri RA. Different combinations of regulatory elements may explain why placenta-specific expression of the glycoprotein hormone q-subunit gene occurs only in primates and horses. Biol Reprod 1991;44:231–237.

    Article  PubMed  CAS  Google Scholar 

  26. Clay CM, Keri RA, Finicle AB, Heckert LL, Hamernik DL, Marschke KM, Wilson EM, French FS, Nilson JR Transcriptional repression of the glycoprotein hormone alpha subunit gene by androgen may involve direct binding of androgen receptor to the proximal promoter. J Biol Chem 1993;268:13556–13564.

    PubMed  CAS  Google Scholar 

  27. Keri RA, Andersen B, Kennedy GC, Hamemik DL, Clay CM, Brace AD, Nett TM, Notides AC, Nilson JR Estradiol inhibits transcription of the human glycoprotein hormone 0-subunit gene despite the absence of a high affinity binding site for estrogen receptor. Mol Endocrinol 1991;5:725–733.

    Article  PubMed  CAS  Google Scholar 

  28. Heckert LL, Wilson EM, Nilson JH. Transcriptional repression of the alpha-subunit gene by androgen receptor occurs independently of DNA binding but requires the DNA- binding and ligand-binding domains of the receptor. Mol Endocrinol 1997;11:1497–1506.

    Article  PubMed  CAS  Google Scholar 

  29. Ken RA, Wolfe MW, Saunders TL, Anderson I, Kendall S, Wagner T, Yeung J, Gorski J, Nett TM, Camper SA, Nilson JH. The proximal promoter of the bovine luteinizing hormone 13-subunit gene confers gonadotrope-specific expression and regulation by gonadotropin-releasing hormone, testosterone, and 1713-estradiol in transgenic mice. Mol Endocrinol 1994;8:1807–1816.

    Article  Google Scholar 

  30. Abbud RA, Ameduri RK, Rao JS, Nett TM, Nile JR Chronic hypersecretion of luteinizing hormone in transgenic mice selectively alms responsiveness of the alpha-subunit gene to gonadotropin-releasing hormone and estrogens. Mol Endocrinol 1999;13:1449–1459.

    Article  PubMed  CAS  Google Scholar 

  31. Flaws JA, Abbud R, Mann RJ, Nilson JH, HirshMl AN. Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary. Biol Rep rod 1997;57:1233–1237.

    Article  CAS  Google Scholar 

  32. Mann RJ, Keri RA, Nilson JH Transgenic mice with chronically elevated lut; netting hormone are infertile due to anovulation, defects in uterine receptivity, and midgestation pregnancy failure. Endocrinology 1999;140:2592–2601.

    Article  PubMed  CAS  Google Scholar 

  33. Gocze PM, Beamer WG, de Jong FH, Freeman DA. Hormone synthesis and responsiveness of spontaneous granulosa cell tumors in (SWR x SWX~9) Fl mice. Gynecol Oncol 1997;65:143–148.

    Article  PubMed  CAS  Google Scholar 

  34. Joshi R, Dunaif A. Ovarian disorders of pregnancy. Endocrinol Metab Clin North Am 1995;24:153–169.

    PubMed  CAS  Google Scholar 

  35. Beamer WG, Hoppe PC, Whitten WK. Spontaneous malignant granulosa cell tumors in ovaries of young SWR mice. Cancer Res 1985;45:5575–5581.

    PubMed  CAS  Google Scholar 

  36. Beamer WG. Gonadotropin, steroid, and thyroid hormone milieu of young SWR mice bearing spontaneous granulosa cell tumors. J Nail Cancer Inst 1986;77:1117–1123.

    CAS  Google Scholar 

  37. Beamer WG, Tennent BJ, Shultz KL, Nadeau JH, Shultz LD, Skow LC. Gene for ovarian granulosa cell tumor susceptibility, Gct, in SWXJ recombinant inbred strains of mice revealed by dehydroepiandrosterone. Cancer Res 1988;48:5092–5095.

    PubMed  CAS  Google Scholar 

  38. Beamer WG, Shultz KL, Tennent BJ. Induction of ovarian granulosa cell tumors in SWXJ-9 mice with dehydroepiandrosterone. Cancer Res 1988;48;2788–2792.

    PubMed  CAS  Google Scholar 

  39. Beamer WG, Shultz KL, Tennent BJ, Azumi N, Sundberg JP. Mouse model for malignant juvenile ovarian granulosa cell tumors. Toxicol Pathol1998;26:704–710.

    PubMed  CAS  Google Scholar 

  40. Beamer WG, Shultz KL, Tennent BJ, Nadeau JH, Churchill GA, Eicher EM. Multigenic and imprinting control of ovarian granulosa cell tumorigenesis in mice. Cancer Res 1998;58:3694–3699.

    PubMed  CAS  Google Scholar 

  41. Tennent BJ, Beamer WG, Shultz LD, Adamson ED. Epidermal growth factor receptors in spontaneous ovarian granulosa cell tumors of SWR-derived mice. Int J Cancer 1989;44:477–482.

    Article  PubMed  CAS  Google Scholar 

  42. Tennent BJ, Shultz KL, Sundberg JP, Beamer WG. Ovarian granulosa cell tumorigenesis in SWR-derived Fl hybrid mice: preneoplastic follicular abnormality and malignant disease progression. Am J Obstet Gynecol 1990;163:625–634.

    PubMed  CAS  Google Scholar 

  43. Beamer WG, Shultz KL, Tennent BJ, Shultz LD. Granulosa cell tumorigenesis in genetically hypogonadal-immunodeficient mice grafted with ovaries from tumor-susceptible donors. Cancer Res 1993;53:3741–3746.

    PubMed  CAS  Google Scholar 

  44. Gell JS, Stannard MW, Ramnani DM, Bradshaw KD. Juvenile granulosa cell tumor in a 13-year-old girl with enchondromatosis (Oilier’s disease): a case repurt. J Pediatr Adolesc Gynecol 1998;11(3):147–150.

    PubMed  CAS  Google Scholar 

  45. Lancaster EJ, Muthuphei MN. Bilateral juvenile granulosa-cell tumour with multiple metastases. A case report. Cent Afr J Med 1998;44:158–160.

    CAS  Google Scholar 

  46. Guthrie MJ. Tumorigenesis in intrasplenic ovaries in mice. Cancer 1957;10:190–203.

    Article  PubMed  CAS  Google Scholar 

  47. Armuth V, Berenblum I. Mechanism of ovarian carcinogenesis: effect of 7,12dimethylbenz[a]anthracene administration on intrasplenic ovarian grafts in unilaterally ovariectomized C3HeB/Fe mice. J Natl Cancer Inst 1979;63:1047–1050.

    PubMed  CAS  Google Scholar 

  48. Capen CC, Beamer WG, Tennent BJ, Stitzel KA. Mechanisms of hormone-mediated carcinogenesis of the ovary in mice. Mutat Res 1995;333:143–151.

    Article  PubMed  CAS  Google Scholar 

  49. Hilfiich J. Comparative morphological studies on the carcinogenic effect of 7,12dimethylbenz(A)anthracene (DMBA) in normal or intrasplenic ovarian tissue of C3H mice. Br J Cancer 1975;32:588–595.

    Article  Google Scholar 

  50. Rao AR. Effects of carcinogen and/or mutagen on normal and gonatotropin-primed ovaries of mice. Int J Cancer 1981;28:105–110.

    Article  PubMed  CAS  Google Scholar 

  51. Taguchi O, Michael SD, Nishizuka Y. Rapid induction of ovarian granulosa cell tumors by 7,12- dimethylbenz(a)anthracene in neonatally estrogenized mice. Cancer Res 1988;48:425–429.

    PubMed  CAS  Google Scholar 

  52. Tennent BJ, Beamer WG. Ovarian tumors not induced by irradiation and gonadotropins in hypogonadal (hpg) mice. Biol Reprod 1986;34:751–760.

    Article  PubMed  CAS  Google Scholar 

  53. Nishizuka Y, Sakakura T, Taguchi O. Mechanism of ovarian tumorigenesis in mice after neonatal thymectomy. Natl Cancer Inst Monogr 1979;51:89–96.

    PubMed  Google Scholar 

  54. Michael SD, Taguchi O, Nishizuka Y. Hormonal characterization of female SL/Ni mice: a small thymus gland strain exhibiting ovarian dysgenesis. J Reprod Immunol 1988;12;277–286.

    Article  PubMed  CAS  Google Scholar 

  55. Michael SD, Taguchi O, Nishizuka Y. Changes in hypophyseal hormones associated with accelerated aging and tumorigenesis of the ovaries in neonatally thymectomized mice. Endocrinology 1981;108:2375–2380.

    Article  PubMed  CAS  Google Scholar 

  56. Michael SD, Taguchi O, Nishizuka Y. Effect of neonatal thymectomy on ovarian development and plasma LH, FSH, GH and PRL in the mouse. Biol Reprod 1980;22:343–350.

    PubMed  CAS  Google Scholar 

  57. Fujii K, Watanabe M. Comparative study of tumorigenicity in mice administered transplacentally or neonatally with metabolites of tryptophan and its related compounds. J Cancer Res Clin Oncol 1980;96:163–168.

    Article  PubMed  CAS  Google Scholar 

  58. Michael SD, De Angelo L, Kaikis-Astaras A. Plasma protein and hormone profiles associated with autoimmune oophoritis and ovarian tumorigenesis in neonatally thymectomized mice. Autoimmunity 1990;6:1–12.

    Article  PubMed  CAS  Google Scholar 

  59. Couse JF, Hewitt SC, Bunch DO, Sar M, Walker VR, Davis BJ, Korach KS. Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta. Science 1999;286:2328–2331.

    Article  PubMed  CAS  Google Scholar 

  60. Couse JF, Bunch DO, Lindzey J, Schomberg DW, Korach KS. Prevention of the polycystic ovarian phenotype and characterization of ovulatory capacity in the estrogen receptor-alpha knockout mouse. Endocrinology 1999;140:5855–5865.

    Article  PubMed  CAS  Google Scholar 

  61. Fisher CR, Graves KH, Parlow AF, Simpson ER. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cypl 9 gene. Proc Nail Acad Sci USA 1998;95:6965–6970.

    Article  CAS  Google Scholar 

  62. Matzuk MM, Finegold MJ, Su JG, Hsueh AJ, Bradley A. Alpha-inhibin is a tumour.. suppressor gene with gonadal specificity in mice. Nature 1992;260:313–319.

    Article  Google Scholar 

  63. Kumar TR, Wang Y, Matzuk MM. Gonadotropins are essential modifier factors for gonadal tumor development in inhibin-deficient mice. Endocrinology 1996;137:4210–4216.

    Article  PubMed  CAS  Google Scholar 

  64. Kumar TR, Wang Y, Lu N, Matzuk MM. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Gen 1997;15:201–204.

    Article  CAS  Google Scholar 

  65. Kumar TR, Palapattu G, Wang P, Woodruff TK, Boime I, Byrne MC, Matzuk MM. Transgenic models to study gonadotropin function: the role of follicle-stimulating hormone in gonadal growth and tumorigenesis. Mol Endocrinol 1999;13:851–865.

    Article  PubMed  CAS  Google Scholar 

  66. Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, Sar M, Korach KS, Gustafsson JA, Smithies O. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci USA 1998;95:15677–15682.

    Article  PubMed  CAS  Google Scholar 

  67. Keri RA, Lozada KL, Abdul-Karim FW, Nadeau JH, Nilson JH. Luteinizing hormone induction of ovarian tumors: oligogenic differences between mouse strains dictates tumor disposition. Proc Nail Acad Sci USA 2000;97:383–387.

    Article  CAS  Google Scholar 

  68. Lee WL, Yuan CC, Lai CR, Wang PH. Hemoperitoneum is an initial presentation of recurrent granulosa cell tumors of the ovary. Jpn J Clin Oncol 1999;29:509–512.

    Article  PubMed  CAS  Google Scholar 

  69. Fontanelli R, Stefanon B, Raspagiesi F, Kenda R, Tomasic G, Spatti G, Riboldi G, Di Donato P, Pilotti S, De Palo G. Adult granulosa cell tumor of the ovary: a clinico pathologic study of 35 cases. Tumori 1998;84:60–64.

    PubMed  CAS  Google Scholar 

  70. Zheng W, Lu JJ, Luo F, Zheng Y, Feng Y, Felix JC, Lauchlan SC, Pike MC. Ovarian epithelial tumor growth promotion by follicle-stimulating hormone and inhibition of the effect by luteinizing hormone. Gynecol Oncol 2000;76:80–88.

    Article  PubMed  CAS  Google Scholar 

  71. Zheng W, Magid MS, Kramer EE, Chen YT. Follicle-stimulating hormone receptor is expressed in human ovarian surface epithelium and fallopian tube. Am J Pathol 1996;148:47–53.

    PubMed  CAS  Google Scholar 

  72. Stouffer RL, Grodin MS, Davis JR, Surwit EA. Investigation of binding sites for follicle-stimulating hormone and chorionic gonadotropin in human ovarian cancers. J Clin Endocrinol Metab 1984;59:441–446.

    Article  PubMed  CAS  Google Scholar 

  73. Burger HG, Baillie A, Drummond AE, Healy DL, Jobling T, Mamers P, Robertson DM, Susil B, Cahir N, Shen Y, Verity K, Fuller PJ, Groome NP, Findlay X. Inhibin and ovarian cancer. J Reprod Immunol 1998;39:77–87.

    Article  PubMed  CAS  Google Scholar 

  74. Robertson DM, Cahir N, Burger HG, Mamers P, Groome N. Inhibin forms in serum from postmenopausal women with ovarian cancers. Clin Endocrinol 1999;50:381–386.

    Article  CAS  Google Scholar 

  75. Robertson DM, Cahir N, Burger HG, Mamers P, McCloud PI, Pettersson K, McGuckin M. Combined inhibin and CAl25 assays in the detection of ovarian cancer. Clin Chem 1999;45:651–658.

    PubMed  CAS  Google Scholar 

  76. Lane AH, Lee MM, Fuller AF, Jr., Kehas DJ, Donahoe PK, MacLaughlin DT. Diagnostic utility of Mullerian inhibiting substance determination in patients with primary and recurrent granulosa cell tumors. Gynecol Oncol 1999;73:51–55.

    Article  PubMed  CAS  Google Scholar 

  77. Meyer JS, Rao BR, Valdes R, Jr., Burstein R, Wasserman HC. Progesterone receptor in granulosa cell tumor. Gynecol Oncol 1982;13:252–257.

    Article  PubMed  CAS  Google Scholar 

  78. Avizienyte E, Loukola A, Roth S, Hemminki A, Tarkkanen M, Salovaara R, Arola J, Butzow R, Husgafvel-Pursiainen K, Kokkola A, Jarvinen H, Aaltonen LA. LKB1 somatic mutations in sporadic tumors. Am J Pathol 1999;154:677–681.

    Article  PubMed  CAS  Google Scholar 

  79. Wang ZJ, Churchman M, Campbell IG, Xu WH, Yan ZY, McCluggage WG, Foulkes WD, Tomlinson IP. Allele loss and mutation screen at the Peutz-Jeghers (LKB1) locus (19p13.3) in sporadic ovarian tumours. Br J Cancer 1999;80:70–72.

    Article  PubMed  CAS  Google Scholar 

  80. Wemess BA, Afify AM, Eltabbakh GH, Huelsman K, Piver MS, Paterson JM. p53, e-erbB, and Ki-67 expression in ovaries removed prophylactically from women with a family history of ovarian cancer. Int J Gynecol Pathol 1999;18:338–343.

    Article  Google Scholar 

  81. Van dB I, Dal Cin P, De Groef K, Michielssen P, Van den BH. Monosomy 22 and trisomy 14 may be early events in the tumorigenesis of adult granulosa cell tumor. Cancer Genet Cytogenet 1999;112:46–48.

    Article  Google Scholar 

  82. Tanyi J, Rigo J, Jr., Csapo Z, Szentirmay Z. Trisomy 12 in juvenile granulosa cell tumor of the ovary during pregnancy. A report of two cases. J Reprod Med 1999;44:826–832.

    PubMed  CAS  Google Scholar 

  83. Wise PM, Kashon ML, Krajnak KM, Rosewell KL, Cai A, Scarbrough K, Hamey JP, McShane T, Lloyd JM, Weiland NG. Aging of the female reproductive system: a window into brain aging. Recent Prog Hotta Res 1997;52:279–303.

    CAS  Google Scholar 

  84. Wise PM, Krajnak KM, Kashon ML. Menopause: the aging of multiple pacemakers. Science 1996;273:67–70.

    Article  PubMed  CAS  Google Scholar 

  85. Mosgaard BJ, Lidegaard O, Kjaer SK, Schou G, Andersen AN. Infertility, fertility drugs, and invasive ovarian cancer: a case-control study. Fertil Steril 1997;67:1005–1012.

    Article  PubMed  CAS  Google Scholar 

  86. Bristow RE, Karlan BY. Ovulation induction, infertility, and ovarian cancer risk. Fertil Steril 1996;66:499–507.

    PubMed  CAS  Google Scholar 

  87. Willemsen W, Kruitwagen R, Bastiaans B, Hanselaar T, Rolland R. Ovarian stimulation and granulosa-cell tumour. Lancet 1993;341:986–988.

    Article  PubMed  CAS  Google Scholar 

  88. Rossing MA, Daling JR, Weiss NS, Moore DE, Self SG. Ovarian tumors in a cohort of infertile women. N Engl J Med 1994;331:771–776.

    Article  PubMed  CAS  Google Scholar 

  89. Venn A, Watson L, Lumley J, Giles G, King C, Healy D. Breast and ovarian cancer incidence after infertility and in vitro fertilisation. Lancet 1995;346:995–1000.

    Article  PubMed  CAS  Google Scholar 

  90. Unkila-Kallio L, Leminen A, Tiitinen A, Ylikorkala O. Nationwide data on falling incidence of ovarian granulosa cell tumours concomitant with increasing use of ovulation inducers. Hum Reprod 1998;13:2828–2830.

    Article  PubMed  CAS  Google Scholar 

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  1. School of Medicine, Dept. of Pharmacology, Case Western Reserve University, Cleveland, OH

    Gabe E. Owens, Ruth A. Keri & John H. Nilson

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  1. Gabe E. Owens
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  2. Ruth A. Keri
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  3. John H. Nilson
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  1. The University of Manchester, UK

    Maria G. Castro Ph.D.

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Owens, G.E., Keri, R.A., Nilson, J.H. (2001). LH Hypersecreting Mice: A Model for Ovarian Granulosa Cell Tumors. In: Castro, M.G. (eds) Transgenic Models in Endocrinology. Endocrine Updates, vol 13. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1633-0_4

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