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Suppression of Aromatase Activity in Polycystic Ovary Syndrome

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Book cover Polycystic Ovary Syndrome

Part of the book series: Serono Symposia USA ((SERONOSYMP))

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Abstract

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in women of childbearing age. Estimates of incidence based on ultrasound scans of normal populations suggest that up to 23% of normal women may have polycystic ovaries (1); however, not all of these women are anovulatory or require medical treatment. The majority of the women with ultrasound evidence of PCOS have irregular menstrual cycles (75%) and 75% of the women with regular cycles are hirsute. This is in contrast to the women with normal ovaries (no ultrasound evidence of polycystic ovaries) of whom only.9% have irregular cycles (2). Within the infertile population, approximately three quarters of women with anovulatory infertility have PCO, thus accounting for approximately one third of women with secondary amenorrhea and approximately 90% of women with oligomenorrhea (3). Clearly PCOS affects a large number of women and is associated with menstrual irregularities in a large proportion of women.

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References

  1. Polson DW, Adams J, Wadsworth J, Franks S. Polycystic ovaries—a common finding in normal women. Lancet 1988; 1: 870–2.

    Article  PubMed  CAS  Google Scholar 

  2. Franks S. Polycystic ovary syndrome: a changing perspective. Clin Endocrinol 1989; 31: 87–120.

    Article  CAS  Google Scholar 

  3. Franks S, White DM. Prevalence of and etiological factors in polycystic ovarian syndrome. Ann NY Acad Sci 1993; 687: 112–4.

    Article  PubMed  CAS  Google Scholar 

  4. Conway GS, Agrawal R, Betteridge DJ, Jacobs HS. Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome. Clin Endocrinol 1992; 37: 119–25.

    Article  CAS  Google Scholar 

  5. Dahlgren E, Janson PO, Johansson S, Lapidus L, Oden A. Polycystic ovary syndrome and risk for myocardial infarction: evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 1992; 71: 599–604.

    Article  PubMed  CAS  Google Scholar 

  6. Smyczek-Gargya B, Geppert M. Endometrial cancer associated with polycystic ovaries in young women. Pathol Res Pract 1992; 188: 946–8.

    Article  PubMed  CAS  Google Scholar 

  7. Hughesdon PE. Morphology and morphogenesis of the Stein-Leventhal ovary and so called “hyperthecosis.” Obstet Gynecol Sury 1982; 37: 59–77.

    Article  CAS  Google Scholar 

  8. Yen SSC. The polycystic ovary syndrome. Clin Endocrinol 1980; 12: 177–208.

    Article  CAS  Google Scholar 

  9. Erickson GF. Polycystic ovary syndrome: normal and abnormal steroidogenesis. In: Schats R, Schoemaker J, eds. Ovarian endocrinopathies. London: Parthenon Publishing, 1994: 103–15.

    Google Scholar 

  10. Zeleznik AJ, Fairchild-Benyo D. Control of follicular development, corpus luteum function, and the recognition of pregnancy in higher primates. In: Knobil E, Neill JD, eds. The physiology of reproduction. New York: Raven Press, 1994: 751–82.

    Google Scholar 

  11. McNatty KP, Baird DT. Relationship between follicle-stimulating hormone, androstenedione and oestradiol in human follicular fluid. J Endocrinol 1978; 76: 527–31.

    Article  PubMed  CAS  Google Scholar 

  12. Hedin L, Rodgers RJ, Simpson ER, Richards JS. Changes in content of cytochrome P45017α, cytochrome P450ssc, and 3-hydroxy-3-methylglutary CoA reductase in developing rat ovarian follicles and corpora lutea: correlation with theca cell steroidogenesis. Biol Reprod 1987; 37: 211–23.

    Article  PubMed  CAS  Google Scholar 

  13. Bogovich K, Richards JS. Androgen biosynthesis in developing ovarian follicles: evidence that luteinizing hormone regulates thecal 17α-hydroxylase and C17–20-lyase activities. Endocrinology 1982; 111: 1201–8.

    Article  PubMed  CAS  Google Scholar 

  14. Gelety TJ, Magoffin DA. Ontogeny of steroidogenic enzyme gene expression in the theca interna of developing ovarian follicles. In: Society for Gynecologic Investigation, 1994, Abstract 125.

    Google Scholar 

  15. Magoffin DA, Weitsman SR. Differentiation of ovarian theca-interstitial cells in vitro: regulation of 17α-hydroxylase messenger ribonucleic acid expression by luteinizing hormone and insulin-like growth factor-I. Endocrinology 1993; 132: 1945–51.

    Article  PubMed  CAS  Google Scholar 

  16. Magoffin DA, Weitsman SR. Insulin-like growth factor-I stimulates the expression of 3β-hydroxysteroid dehydrogenase messenger ribonucleic acid in ovarian theca-interstitial cells. Biol Reprod 1993; 48: 1166–73.

    Article  PubMed  CAS  Google Scholar 

  17. Magoffin DA, Weitsman SR. Effect of insulin-like growth factor-I on cholesterol side chain cleavage cytochrome P450 messenger ribonucleic acid expression in ovarian theca-interstitial cells stimulated to differentiate in vitro. Mol Cell Endocrinol 1993; 96: 45–51.

    Article  PubMed  CAS  Google Scholar 

  18. Magoffin DA, Weitsman SR. Insulin-like growth factor-I regulation of luteinizing hormone (LH) receptor messenger ribonucleic acid expression and LH-stimulated signal transduction in rat ovarian theca-interstitial cells. Biol Reprod 1994; 51: 766–75.

    Article  PubMed  CAS  Google Scholar 

  19. Smyth CD, Miro F, Whitelaw PF, Howles CM, Hillier SG. Ovarian thecal/ interstitial androgen synthesis is enhanced by a follicle-stimulating hormone-stimulated paracrine mechanism. Endocrinology 1993; 133: 1532–8.

    Article  PubMed  CAS  Google Scholar 

  20. Hillier SG, Yong EL, Illingworth PJ, Baird DT, Schwall RH, Mason AJ. Effect of recombinant inhibin on androgen synthesis in cultured human thecal cells. Mol Cell Endocrinol 1991; 75: R1–6.

    Article  PubMed  CAS  Google Scholar 

  21. Erickson GF, Hsueh AJW, Quigley ME, Rebar RW, Yen SSC. Functional studies of aromatase activity in human granulosa cells from normal and polycystic ovaries. J Clin Endocrinol Metab 1979; 49: 514–9.

    Article  PubMed  CAS  Google Scholar 

  22. Erickson GF, Magoffin DA, Garzo VG, Cheung AP, Chang RJ. Granulosa cells of polycystic ovaries: are they normal or abnormal? Hum Reprod 1992; 7: 293–9.

    PubMed  CAS  Google Scholar 

  23. Erickson GF, Magoffin DA, Cragun JR, Chang RJ. The effects of insulin and insulin-like growth factors-I and -II on estradiol production by granulosa cells of polycystic ovaries. J Clin Endocrinol Metab 1990; 70: 894–902.

    Article  PubMed  CAS  Google Scholar 

  24. San Roman GA, Magoffin DA. Insulin-like growth factor binding proteins in ovarian follicles from women with polycystic ovarian disease: cellular source and levels in follicular fluid. J Clin Endocrinol Metab 1992; 75: 1010–6.

    Article  PubMed  CAS  Google Scholar 

  25. Tamura T, Kitawaki J, Yamamoto T, Osawa Y, Kominami S, Takemori S, Okada H. Immunohistochemical localization of 17α-hydroxylase/C17–20 lyase and aromatase cytochrome P-450 in polycystic human ovaries. J Endocrinol 1993; 139: 503–9.

    Article  PubMed  CAS  Google Scholar 

  26. Yamoto M, Minami S, Nakano R. Immunohistochemical localization of inhibin subunits in polycystic ovary. J Clin Endocrinol Metab 1993; 77: 859–62.

    Article  PubMed  CAS  Google Scholar 

  27. Pache TD, Hop WCJ, De Jong FH, Leerentveld RA, van Geldorp H, Van de Kamp TMM, Gooren LJG, Fauser BCJM. 17β-oestradiol, androstenedione and inhibin levels in fluid from individual follicles of normal and polycystic ovaries, and in ovaries from androgen treated female to male transsexuals. Clin Endocrinol 1992; 36: 565–71.

    Article  CAS  Google Scholar 

  28. Lambert-Messerlain GM, Hall JE, Sluss PM, Taylor AE, Martin KA, Groome NP, Crowley WF, Schneyer AL. Relatively low levels of dimeric inhibin circulate in men and women with polycystic ovarian syndrome using a specific two-site enzyme-linked immunosorbent assay. J Clin Endocrinol Metab 1994; 79: 45–50.

    Article  Google Scholar 

  29. Eden JA, Jones J, Carter GD, Alaghband-Zadeh J. Follicular fluid concentrations of insulin-like growth factor 1, epidermal growth factor, transforming growth factor-alpha and sex-steroids in volume matched normal and polycystic human follicles. Clin Endocrinol 1990; 32: 395–405.

    Article  CAS  Google Scholar 

  30. Erickson GF, Garzo VG, Magoffin DA. Insulin-like growth factor-I (IGF-I) regulates aromatase activity in human granulosa and granulosa luteal cells. J Clin Endocrinol Metab 1989; 69: 716–24.

    Article  PubMed  CAS  Google Scholar 

  31. Hillier SG, Yong EL, Illingsworth PJ, Baird DT, Schwall RH, Mason AJ. Effect of recombinant activin on androgen synthesis in cultured human thecal cells. J Clin Endocrinol Metab 1991; 72: 1206–11.

    Article  PubMed  CAS  Google Scholar 

  32. Iwashita M, Mimuro T, Watanabe M, Setoyama T, Matsuo A, Adachi T, Takeda Y, Sakamoto S. Plasma levels of insulin-like growth factor-I and its binding protein in polycystic ovary syndrome. Horm Res 1990; 33: 21–6.

    Article  PubMed  CAS  Google Scholar 

  33. San Roman GA, Magoffin DA. Insulin-like growth factor binding proteins in healthy and atretic follicles during natural menstrual cycles. J Clin Endocrinol Metab 1993; 76: 625–32.

    Article  PubMed  CAS  Google Scholar 

  34. Franks S, Mason HD. Polycystic ovary syndrome: interaction of follicle stimulating hormone and polypeptide growth factors in oestradiol production by human granulosa cells. J Steroid Biochem Mol Biol 1991; 40: 405–9.

    Article  PubMed  CAS  Google Scholar 

  35. Mason HD, Margara R, Winston RML, Beard RW, Reed MJ, Franks S Inhibition of oestradiol production by epidermal growth factor in human granulosa cells on normal and polycystic ovaries. Clin Endocrinol 1990; 33: 511–7.

    Article  CAS  Google Scholar 

  36. Volpe A, Coukos G, D’Ambrogio G, Artini PG, Genazzani AR. Follicular fluid steroid and epidermal growth factor content, and in vitro estrogen release by granulosa-luteal cells from patients with polycystic ovaries in an IVF/ET program. Eur J Obstet Gynecol Reprod Biol 1991; 42: 195–9.

    Article  PubMed  CAS  Google Scholar 

  37. Agarwal SK, Judd HL, Magoffin DA. A mechanism for suppression of estrogen in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1996;81: in press.

    Google Scholar 

  38. Rosenfield RL, Barnes RB, Cara JF, Lucky AW. Dysregulation of cytochrome P450c17α as the cause of polycystic ovarian syndrome. Fertil Steril 1990; 53: 785–91.

    PubMed  CAS  Google Scholar 

  39. Stewart PM, Shackleton CHL, Beastall GH, Edwards CRW. 5α-reductase activity in polycystic ovary syndrome. Lancet 1990; 335: 431–3.

    Article  PubMed  CAS  Google Scholar 

  40. McNatty KP, Makris A, Reinhold VN, DeGrazia C, Osathanondh R, Ryan KJ. Metabolism of androstenedione by human ovarian tissues in vitro with particular reference to reductase and aromatase activity. Steroids 1979; 34: 429–43.

    Article  PubMed  CAS  Google Scholar 

  41. Hillier SG, van den Boogaard AMJ, Reichert LE, van Hall EV. Intraovarian sex steroid hormone interactions and the regulation of follicular maturation: aromatization of androgens by human granulosa cells in vitro. J Clin Endocrinol Metab 1980; 50: 640–7.

    Article  PubMed  CAS  Google Scholar 

  42. Hillier SG, van den Boogaard AM, Reichert LE, van Hall EV. Alterations in granulosa cell aromatase activity accompanying preovulatory follicular development in the rat ovary with evidence that 5alpha-reduced C19 steroids inhibit the aromatase reaction in vitro. J Endocrinol 1980; 84: 409–19.

    Article  PubMed  CAS  Google Scholar 

  43. Harlow CR, Shaw HJ, Hillier SG, Hodges JK. Factors influencing follicle-stimulating hormone-responsive steroidogenesis in marmoset granulosa cells: effects of androgens and the stage of follicular maturity. Endocrinology 1988; 122: 2780–7.

    Article  PubMed  CAS  Google Scholar 

  44. Poretsky L, Piper B. Insulin resistance, hypersecretion of LH, and a dual-defect hypothesis for the pathogenesis of polycystic ovarian syndrome. Obstet Gynecol 1994; 84: 613–21.

    PubMed  CAS  Google Scholar 

  45. Dunaif A. Insulin resistance in polycystic ovarian syndrome. Ann NY Acad Sci 1993; 687: 60–4.

    Article  PubMed  CAS  Google Scholar 

  46. Barbieri RL, Smith S, Ryan KJ. The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertil Steril 1988; 50: 197–212.

    PubMed  CAS  Google Scholar 

  47. Dunaif A. Adrenal disorders and polycystic ovary syndrome. Horm Res 1992; 37: 39–44.

    Article  PubMed  Google Scholar 

  48. Tsuji M, Terada N, Yabumoto H, Takeyama M, Matsumoto K. Hormonal regulation of activites of 4-ene-5β and 5α-reductases and 17β-ol-dehydrogenase in immature golden hamster ovary. J Steroid Biochem 1983; 18: 777–81.

    Article  PubMed  CAS  Google Scholar 

  49. George FW, Russell DW, Wilson JD. Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5α-reductase. Proc Natl Acad Sci USA 1991; 88: 8044–7.

    Article  PubMed  CAS  Google Scholar 

  50. Horton R, Pasupuletti V, Antonipillai I. Androgen induction of steroid 5areductase may be mediated via insulin-like growth factor-I. Endocrinology 1993; 133: 447–51.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Denis A. Magoffin
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  2. Sanjay K. Agarwal
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  3. Artur J. Jakimiuk
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Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynecology, School of Medicine, University of California, Davis, 95816, Sacramento, CA, USA

    R. Jeffrey Chang M.D.

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© 1996 Springer-Verlag New York, Inc.

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Magoffin, D.A., Agarwal, S.K., Jakimiuk, A.J. (1996). Suppression of Aromatase Activity in Polycystic Ovary Syndrome. In: Chang, R.J. (eds) Polycystic Ovary Syndrome. Serono Symposia USA. Springer, New York, NY. https://doi.org/10.1007/978-1-4613-8483-0_14

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  • DOI: https://doi.org/10.1007/978-1-4613-8483-0_14

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4613-8485-4

  • Online ISBN: 978-1-4613-8483-0

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