Download PDF
Exp Clin Endocrinol Diabetes 2005; 113(2): 115-121
DOI: 10.1055/s-2004-830540
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Role of Ovary and Adrenal Glands in Hyperandrogenemia in Patients with Polycystic Ovary Syndrome

N. Kamel1 , V. Tonyukuk1 , R. Emral1 , D. Çorapçıoğlu1 , M. Baştemir1 , S. Güllü1
  • 1Ankara University, School of Medicine, Department of Endocrinology and Metabolic Diseases, Ankara, Turkey
Further Information

Publication History

Received: November 4, 2003 First decision: March 3, 2004

Accepted: September 9, 2004

Publication Date:
17 March 2005 (online)

Also available at
    Permissions and Reprints

Abstract

Ovary is the main source of the hyperandrogenism in polycystic ovary syndrome (PCOS). Adrenal glands may also be involved in the pathogenesis of the development of PCOS. To investigate this possibility and to find out if buserelin test is able to distinguish PCOS patients from the patients with idiopathic hirsutism (IH), ACTH and buserelin tests were performed in 29 women with PCOS, 21 women with IH, and 20 control subjects (CS). We also aimed to determine the role of dysregulation of 17 hydroxylase in the development of PCOS.

Basal and stimulated dehydroepiandrosterone sulfate (DHEA-S) and stimulated cortisol (F) levels after ACTH administration were significantly higher in PCOS group than in IH and CS groups (p < 0.0001 and p < 0.05, respectively). PCOS patients also possessed significantly higher basal and stimulated 17-hydroxyprogesterone (17-OH P) levels, including the peak levels (p < 0.02), during buserelin testing when compared with IH patients and CS. There was no significant correlation between the ACTH-stimulated and the buserelin-stimulated peak 17-OH P values.

In conclusion, significantly higher basal and ACTH-stimulated levels of F and DHEA-S in PCOS compared with controls and patients with IH, reflect that adrenal hyperactivity also plays a role in hyperandrogenemia seen in PCOS. Because of the lack of the correlation between ACTH-stimulated and buserelin-stimulated 17-OH P levels, it is hard to say that adrenal hyperactivity seen in PCOS is the result of the dysregulation of cytochrome P450c17-α enzyme. Our results suggest that buserelin test which is an GnRH analogue could distinguish at least some of the patients with PCOS from the other patients presenting with the common symptoms of hyperandrogenemia.

Key words

Polycystic ovary syndrome - ovary - adrenal gland - buserelin stimulation test

References

  • 1 Azziz R, Boots L R, Parker Jr C R, Bradley Jr E, Zacur H A. 11 beta-hydroxylase deficiency in hyperandrogenism.  Fertil Steril. 1991;  55 733-741
    PubMedGoogle Scholar
  • 2 Azziz R, Bradley Jr E L, Potter H D, Boots L R. Adrenal androgen excess in women: lack of a role for 17-hydroxylase and 17, 20 lyase dysregulation.  J Clin Endocrinol Metab. 1995;  80 400-405
    CrossrefPubMedGoogle Scholar
  • 3 Azziz R, Rafi A, Smith B R, Bradley Jr E L, Zacur H A. On the origin of the elevated 17-hydroxyprogesterone levels after adrenal stimulation in hyperandrogenism.  J Clin Endocrinol Metab. 1990;  70 431-436
    PubMedGoogle Scholar
  • 4 Azziz R, Rittmaster R S, Fox L M, Bradley Jr E L, Potter H D, Boots L R. Role of the ovary in the adrenal androgen excess of hyperandrogenic women.  Fertil Steril. 1998;  69 851-859
    CrossrefPubMedGoogle Scholar
  • 5 Barnes R B, Rosenfield R L, Burstein S, Ehrmann D A. Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome.  N Engl J Med. 1989;  320 559-565
    PubMedGoogle Scholar
  • 6 Chetkowski R J, Chang R J, DeFazio J, Meldrum D R, Judd H L. Origin of serum progestins in polycystic ovarian disease.  Obstet Gynecol. 1984;  64 27-31
    PubMedGoogle Scholar
  • 7 Ehrmann D A, Barnes R B, Rosenfield R L. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion.  Endocr Rev. 1995;  16 322-353
    CrossrefPubMedGoogle Scholar
  • 8 Ehrmann D A, Rosenfield R L, Barnes R B, Brigell D F, Sheikh Z. Detection of functional ovarian hyperandrogenism in women with androgen excess.  N Engl J Med. 1992;  327 157-162
    CrossrefPubMedGoogle Scholar
  • 9 Erel C T, Senturk L M, Oral E, Colgar U, Ertungealp E. Adrenal androgenic response to 2-hour ACTH stimulation test in women with PCOS.  Gynecol Endocrinol. 1998;  12 223-229
    PubMedGoogle Scholar
  • 10 Hatch R, Rosenfield R L, Kim M H, Tredway D. Hirsutism: implications, etiology, and management.  Am J Obstet Gynecol. 1981;  140 815-830
    Google Scholar
  • 11 Horvath E, Varga B, Stark E. Stimulation of progesterone production by adrenocorticotropic hormone and prostaglandin E2 in rat luteal cells.  Biol Reprod. 1986;  35 44-48
    PubMedGoogle Scholar
  • 12 Ibanez L, Potau N, Zampolli M, Prat N, Gussinye M, Saenger P, Vicens-Calvet E, Carrascosa A. Source localization of androgen excess in adolescent girls.  J Clin Endocrinol Metab. 1994;  79 1778-1784
    CrossrefPubMedGoogle Scholar
  • 13 Kandarakis E D, Dunaif A. New perspectives in polycystic ovary syndrome.  Trends Endocrinol Metab. 1996;  7 267-271
    PubMedGoogle Scholar
  • 14 Keleştimur F, Şahin Y. Alternate pathway 17, 20-lyase enzyme activity in the adrenals is enhanced in patients with polycystic ovary syndrome.  Fertil Steril. 1999;  71 1075-1078
    CrossrefPubMedGoogle Scholar
  • 15 Keleştimur F, Şahin Y, Ayata D, Tutuş A. The prevalence of non-classic adrenal hyperplasia due to 11β-hydroxylase deficiency among hirsute women in a Turkish population.  Clin Endocrinol (Oxford). 1996;  45 381-384
    CrossrefPubMedGoogle Scholar
  • 16 Lewis V. Polycystic ovary syndrome - A diagnostic challenge.  Obstet Gynecol Clin North Am. 2001;  28 1-20
    CrossrefPubMedGoogle Scholar
  • 17 Licht P, Wildt L. Luteal and extraluteal receptors for hCG and LH.  Zentralbl Gynakol. 1998;  120 98-105
    PubMedGoogle Scholar
  • 18 Lin C J, Jorge A A, Latronico A C, Marui S, Fragoso M C, Martin R M, Carvalho F M, Arnhold I J, Mendonca B B. Origin of an ovarian steroid cell tumor causing isosexual pseudoprecocious puberty demonstrated by the expression of adrenal steroidogenic enzymes and adrenocorticotropin receptor.  J Clin Endocrinol Metab. 2000;  85 1211-1214
    CrossrefPubMedGoogle Scholar
  • 19 Martikainen H, Salmela P, Nuojua-Huttunen S, Perala J, Leinonen S, Knip M, Ruokonen A. Adrenal steroidogenesis is related to insulin in hyperandrogenic women.  Fertil Steril. 1996;  66 564-570
    PubMedGoogle Scholar
  • 20 Meikle A W, Worley R J, West C D. Adrenal corticoid hyperresponsiveness in hirsute women.  Fertil Steril. 1984;  41 575-579
    PubMedGoogle Scholar
  • 21 Miller W L. Molecular biology of steroid hormone synthesis.  Endocr Rev. 1988;  9 295-318
    CrossrefPubMedGoogle Scholar
  • 22 Moltz L, Schwartz U. Gonadal and adrenal androgen secretion in hirsute females.  J Clin Endocrinol Metab. 1986;  15 229-245
    PubMedGoogle Scholar
  • 23 Pabon J E, Li X, Lei Z M, Sanfilippo J S, Yussman M A, Rao C V. Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal glands.  Clin Endocrinol Metab. 1996;  81 2397-2400
    CrossrefPubMedGoogle Scholar
  • 24 Rosenfield R L, Barnes R B, Cara J F, Lucky A W. Dysregulation of cytochrome P450c17-α as the cause of polycystic ovarian syndrome.  Fertil Steril. 1990;  53 785-791
    PubMedGoogle Scholar
  • 25 Rosenfield R L, Barnes R B, Ehrmann D A. Studies of the nature of 17 hydroxyprogesterone hyperresponsiveness to gonadotropin-releasing hormone agonist challenge in functional ovarian hyperandrogenism.  J Clin Endocrinol Metab. 1994;  79 1686-1692
    CrossrefPubMedGoogle Scholar
  • 26 Şahin Y, Ayata D, Keleştimur F. Lack of relationship between 17-hydroxyprogesterone response to buserelin testing and hyperinsulinemia in polycystic ovary syndrome.  Eur J Endocrinol. 1997;  136 410-415
    PubMedGoogle Scholar
  • 27 Şahin Y, Keleştimur F. 17-hydroxyprogesterone response to buserelin testing in the polycystic ovary syndrome.  Clin Endocrinol (Oxf). 1993;  39 151-155
    PubMedGoogle Scholar
  • 28 Şahin Y, Keleştimur F. 17-hydroxyprogesterone responses to gonadotrophin-releasing hormone agonist buserelin and adrenocorticotrophin in polycystic ovary syndrome: investigation of adrenal and ovarian cytochrome P450c17-α dysregulation.  Hum Reprod. 1997 a;  12 910-913
    CrossrefPubMedGoogle Scholar
  • 29 Şahin Y, Keleştimur F. The frequency of late-onset 21-hydroxylase and 11 beta-hydroxylase deficiency in women with polycystic ovary syndrome.  Eur J Endocrinol. 1997 b;  137 670-674
    CrossrefPubMedGoogle Scholar
  • 30 Takayama K, Fukaya T, Sasano H, Funayama Y, Suzuki T, Takaya R, Wada Y, Yajima A. Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome.  Hum Reprod. 1996;  11 1387-1392
    PubMedGoogle Scholar
  • 31 Tsilchorozidou T, Honour J W, Conway G S. Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5 alpha-reduction but not the elevated adrenal steroid production rates.  J Clin Endocrinol Metab. 2003;  88 5907-5913
    CrossrefPubMedGoogle Scholar
  • 32 Turner E I, Watson M J, Perry L A, White M C. Investigation of adrenal function in women with oligomenorrhoea and hirsutism (clinical PCOS) from the north-east of England using an adrenal stimulation test.  Clin Endocrinol (Oxford). 1992;  36 389-397
    PubMedGoogle Scholar
  • 33 White D, Leigh A, Wilson C, Donaldson A, Franks S. Gonadotrophin and gonadal steroid response to a single dose of a long-acting agonist of gonadotrophin-releasing hormone in ovulatory and anovulatory women with polycystic ovary syndrome.  Clin Endocrinol (Oxf). 1995;  42 475-481
    PubMedGoogle Scholar

Prof. Dr. Nuri Kamel

Ibn-i Sina Hospital, 10. floor, D block

Samanpazarı

06100 Ankara

Turkey

Phone: + 903123094717

Fax: + 90 31 23 09 45 05

Email: nuri.kamel@temd.org.tr

      >