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Increased expression of P450scc and CYP17 in development of endogenous hyperandrogenism in a rat model of PCOS

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Abstract

The objective of the present study was to characterize the effect of insulin plus hCG on the expression of steroidogenic enzymes (P450scc and CYP17) in polycystic ovaries of rats. Changes in estrous cycle, ovarian morphology, hormonal levels, and protein levels by immunohistochemistry and western-blot were determined. Rats treated with insulin plus hCG displayed abnormal estrous cycles with increasing androgen biosynthesis. Meanwhile, insulin plus hCG resulted in multiple large cysts with diminished granulosa layers and increased thecal layers and stromal–interstitial tissue. Moreover, there was an increase in the expression of P450scc and CYP17 in thecal and stromal cells in our PCOS rat model compared with control rats. These results indicate that administration of insulin with hCG can synergistically result in endogenous hyperandrogenism which may partially upregulate the expression of steroidogenic enzymes in ovarian tissue.

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References

  1. M. Asuncion, R.M. Calvo, J.L. San Millan, J. Sancho et al., A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J. Clin. Endocrinol. Metab. 85(7), 2434–2438 (2000)

    Article  PubMed  CAS  Google Scholar 

  2. R. Azziz, K.S. Woods, R. Reyna et al., The prevalence and feature of the polycystic ovary syndrome in an unselected population. J. Clin. Endocrinol. Metab. 89(6), 2745–2749 (2004)

    Article  PubMed  CAS  Google Scholar 

  3. A. Huang, K. Brennan, R. Azziz, Prevalence of Hyperandrogenemia in the polycystic ovary syndrome diagnosed by the NIH 1990 criteria. Fertil. Steril. 93(6), 1938–1941 (2010)

    Article  PubMed  Google Scholar 

  4. Y. Chen, J. Qiao, L.Y. Yan et al., Selective impairment in glycogen synthase kinase-3 and mitogen-activated protein kinase phosphorylation: comparisons with the hyperandrogenic and the hyperinsulinemic rats. Fertil. Steril. 92(4), 1447–1455 (2009)

    Article  PubMed  CAS  Google Scholar 

  5. R.J. Auchus, The genetics, pathophysiology, and management of human deficiencies of P450c17. Endocrinol. Metab. Clin. N. Am. 30(1), 101–119 (2001)

    Article  CAS  Google Scholar 

  6. F. Durocher, J. Morissette, J. Simard, Genetic linkage mapping of the CYP11A1 gene encoding the cholesterol side-chain cleavage P450scc close to the CYP1A1 gene and D15S204 in the chromosome 15q22.33-q23 region. Pharmacogenetics 8(1), 49–53 (1998)

    Article  PubMed  CAS  Google Scholar 

  7. W.L. Miller, Androgen biosynthesis from cholesterol to DHEA. Mol. Cell. Endocrinol. 198(1–2), 7–14 (2002)

    Article  PubMed  CAS  Google Scholar 

  8. C. Gilling-Smith, H. Story, V. Rogers et al., Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome. Clin. Endocrinol. (Oxf.) 47(1), 93–99 (1997)

    Article  CAS  Google Scholar 

  9. L. Ciotta, A.E. Calogero, M. Farina et al., Clinical, endocrine and metabolic effects of acarbose, an α-glucosidase inhibitor, in PCOS patients with increased insulin response and normal glucose tolerance. Hum. Reprod. 16(10), 2066–2072 (2001)

    Article  PubMed  CAS  Google Scholar 

  10. D. Romualdi, M. Guido, M. Ciampelli et al., Selective effects of pioglitazone on insulin and androgen abnormalities in normo- and hyperinsulinaemic obese patients with polycystic ovary syndrome. Hum. Reprod. 18(6), 1210–1218 (2003)

    Article  PubMed  CAS  Google Scholar 

  11. J.E. Nestler, D.J. Jakubowicz, Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens. J. Clin. Endocrinol. Metab. 82(12), 4075–4079 (1997)

    Article  PubMed  CAS  Google Scholar 

  12. M.H. Lima, L.C. Souza, L.C. Caperuto et al., Up-regulation of the phosphatidylinositol 3-kinase/protein kinase B pathway in the ovary of rats by chronic treatment with hCG and insulin. J. Endocrinol. 190(2), 451–459 (2006)

    Article  PubMed  CAS  Google Scholar 

  13. K. Hogg, J.M. Young, E.M. Oliver et al., Enhanced thecal androgen production is prenatally programmed in an ovine model of polycystic ovary syndrome. J. Endocrinol. 153(1), 450–461 (2012)

    Article  CAS  Google Scholar 

  14. E.R. Hernandez, C.E. Resnick, M.E. Svoboda, Somatomedin-C/insulin-like growth factor-I as an enhancer of androgen biosynthesis by cultured rat ovarian cells. J. Endocrinol. 122(4), 1603–1612 (1988)

    Article  CAS  Google Scholar 

  15. V.L. Nelson, R.S. Legro, J.F. Strauss et al., Augmented androgen production is a stable steroidogenic phenotype of propagated thecal cells from polycystic ovaries. Mol. Endocrinol. 13(6), 946–957 (1999)

    Article  PubMed  CAS  Google Scholar 

  16. L. Poretsky, J. Clemons, K. Bogovich, Hyperinsulinemia and human chorionic gonadotropin synergistically promote the growth of ovarian follicular cyst in rats. Metabolism 41(8), 903–910 (1992)

    Article  PubMed  CAS  Google Scholar 

  17. K. Bogovich, J. Clemons, L. Poretsky, Insulin has a biphasic effect on the ability of human chorionic gonadotropin to induce ovarian cysts in the rat. Metabolism 48(8), 995–1002 (1999)

    Article  PubMed  CAS  Google Scholar 

  18. R.V. Nemade, O. Carrette, W.J. Larsen et al., Involvement of nitric oxide and the ovarian blood follicle barrier in murine follicular cyst development. Fertil. Steril. 78(6), 1301–1308 (2002)

    Article  PubMed  Google Scholar 

  19. M.-T. Lee, B.C. Bruot, W.C. Adams, Hormonal changes during the early development of ovarian cysts in the rat. Biol. Reprod. 35(3), 542–548 (1986)

    Article  PubMed  CAS  Google Scholar 

  20. L. Poretsky, B. Glover, V. Laumas et al., The effects of experimental hyperinsulinemia on steroid secretion, ovarian [125I] insulin binding, and ovarian [125I] insulin-like growth-factor I binding in the rat. Endocrinology 122(2), 581–585 (1988)

    Article  PubMed  CAS  Google Scholar 

  21. G. Zhang, J.C. Garmey, J.D. Veldhuis, Interactive stimulation by luteinizing hormone and insulin of the steroidogenic acute regulatory (StAR) protein and 17alpha-hydroxylase/17,20-lyase (CYP17) genes in porcine theca cells. Endocrinology 141(8), 2735–2742 (2000)

    Article  PubMed  CAS  Google Scholar 

  22. Y. Li, X.Y. Liang, L.N. Wei et al., Study of RNA interference inhibiting rat ovarian androgen biosynthesis by depressing 17alpha-hydroxylase/17,20-lyase activity in vivo. Reprod. Biol. Endocrinol. 17(7), 73 (2009)

    Article  Google Scholar 

  23. M.J. Young, A.S. Mcneilly, Theca: the forgotten cell of the ovarian follicle. Reproduction 140(4), 489–504 (2010)

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work is supported by the National Natural Sciences Foundation of China (No. 81000234) and the Doctoral Fund of Ministry of Education of China (No. 20090001110090).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, No. 49, Huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of China

    Hui Li, Yuan Chen, Li-ying Yan & Jie Qiao

  2. Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, People’s Republic of China

    Hui Li, Yuan Chen, Li-ying Yan & Jie Qiao

  3. Medical Department of Dezhou University, Shandong, People’s Republic of China

    Hui Li

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  1. Hui Li
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  2. Yuan Chen
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  3. Li-ying Yan
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  4. Jie Qiao
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Correspondence to Jie Qiao.

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Li, H., Chen, Y., Yan, Ly. et al. Increased expression of P450scc and CYP17 in development of endogenous hyperandrogenism in a rat model of PCOS. Endocrine 43, 184–190 (2013). https://doi.org/10.1007/s12020-012-9739-3

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  • DOI: https://doi.org/10.1007/s12020-012-9739-3

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