Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Androgen receptor expression in the human vagina under different physiological and treatment conditions

International Journal of Impotence Research volume 25, pages 7–11 (2013)Cite this article

Subjects

Abstract

Recent data report an important role of testosterone (T) in modulating female sexual responses, but little is known about the expression and distribution of androgen receptor (AR) in the human vagina. Therefore, the aims of our study were to evaluate the expression of AR in the human vagina in premenopausal (PrM) and menopausal (M) women and in T-treated women. Vaginal biopsies were obtained from PrM and postmenopausal women and from women with gender identity disorder (female to male (FtM)) receiving exogenous T. AR gene and protein expression levels in vaginal tissues were determined by real-time PCR and western blot analysis, respectively, whereas the localization of AR in vaginal mucosa and stroma was performed by immunohistochemistry. ARs were detected by immunostaining both in the mucosa and stroma. In vaginal mucosa, AR density score decreases with age but does not change with T administration. In stromal tissue, AR density score does not change with age but significantly increases with T administration (P<0.01). AR protein expression was significantly increased in FtM subjects (P<0.001). The expression of AR messenger RNA (mRNA) evaluated by Real-time PCR showed a significantly higher mRNA expression in FtM versus M patients (P<0.01) and in PrM versus M subjects (P<0.05). In conclusion, we found AR protein and mRNA expression both in the epithelium and stroma of the human vagina in all groups of women. A negative correlation exists between age and AR expression in the vaginal mucosa. T administration increases AR expression in both the mucosa and stroma.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Traish AM, Botchevar E, Kim NN . Biochemical factors modulating female genital sexual arousal physiology. J Sex Med 2010; 7: 2925–2946.

    Article  CAS  Google Scholar 

  2. Goldstein I, Alexander JL . Practical aspects in the management of vaginal atrophy and sexual dysfunction in peri-menopausal and postmenopausal women. J Sex Med 2005; 2 (Suppl 3): 154–165.

    Article  Google Scholar 

  3. Pessina MA, Hoyt Jr RF, Goldstein I, Traish AM . Differential regulation of the expression of estrogen, progesterone, and androgen receptors by sex steroid hormones in the vagina: immunohistochemical studies. J Sex Med 2006; 3: 804–814.

    Article  CAS  Google Scholar 

  4. Brotto LA . The DSM diagnostic criteria for hypoactive sexual desire disorder in women. J Sex Med 2010; 7: 2015–2030.

    Article  Google Scholar 

  5. Bolour S, Braunstein G . Testosterone therapy in women: a review. Int J Impot Res 2005; 17: 399–408.

    Article  CAS  Google Scholar 

  6. Traish AM, Kim SW, Stankovic M, Goldstein I, Kim NN . Testosterone increases blood flow and expression of androgen and estrogen receptors in the rat vagina. J Sex Med 2007; 4: 609–619.

    Article  CAS  Google Scholar 

  7. Giuliano F, Pfaus J, Srilatha B, Hedlund P, Hisasue S, Marson L et al. Experimental models for the study of female and male sexual function. J Sex Med 2010; 7: 2970–2995.

    Article  Google Scholar 

  8. Segraves R, Woodard T . Female hypoactive sexual desire disorder: history and current status. J Sex Med 2006; 3: 408–418.

    Article  Google Scholar 

  9. Berman JR, Almeida FG, Jolin J, Raz S, Chaudhuri G, Gonzalez-Cadavid NF . Correlation of androgen receptors, aromatase, and 5-alpha reductase in the human vagina with menopausal status. Fertil Steril 2003; 79: 925–931.

    Article  Google Scholar 

  10. Hodgins MB, Spike RC, Mackie RM, MacLean AB . An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina. Br J Obstet Gynaecol 1998; 105: 216–222.

    Article  CAS  Google Scholar 

  11. Traish AM, Kim N, Min K, Munarriz R, Goldstein I . Role of androgens in female genital sexual arousal: receptor expression, structure, and function. Fertil Steril 2002; 77 (Suppl 4): S11–S18.

    Article  Google Scholar 

  12. Vermeirsch H, Van den Broeck W, Simoens P . Immunolocalization of sex steroid hormone receptors in canine vaginal and vulvar tissue and their relation to sex steroid hormone concentrations. Reprod Fertil Dev 2002; 14: 251–258.

    Article  CAS  Google Scholar 

  13. Pelletier G, Labrie C, Labrie F . Localization of oestrogen receptor alpha, oestrogen receptor beta and androgen receptors in the rat reproductive organs. J Endocrinol 2000; 165: 359–370.

    Article  CAS  Google Scholar 

  14. Ott J, van Trotsenburg M, Kaufmann U, Schrögendorfer K, Haslik W, Huber JC et al. Combined hysterectomy/salpingo-oophorectomy and mastectomy is a safe and valuable procedure for female-to-male transsexuals. J Sex Med 2010; 7: 2130–2138.

    Article  Google Scholar 

  15. Walker RA . Quantification of immunohistochemistry--issues concerning methods, utility and semi-quantitative assessment I. Histopathology 2006; 49: 406–410.

    Article  CAS  Google Scholar 

  16. Kingsberg SA, Simon JA, Goldstein I . The current outlook for testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. J Sex Med 2008; 2 (5 suppl 4): 182–193.

    Article  Google Scholar 

  17. Palacios S . Hypoactive sexual desire disorder and current pharmacotherapeutic options in women. Womens Health (Lond Engl) 2011; 7: 95–107.

    Article  Google Scholar 

  18. Panjari M, Davis SR . DHEA for postmenopausal women: a review of the evidence. Maturitas 2010; 66: 172–179.

    Article  CAS  Google Scholar 

  19. Kennedy TG . Vaginal mucification in the ovariectomized rat in response to 5alpha-pregnane-3,20-dione, testosterone and 5alpha-androstan-17beta-ol-3-one: test for progestogenic activity. J Endocrinol 1974; 61: 293–300.

    Article  CAS  Google Scholar 

  20. Traish AM, Kim NN, Huang YH, Min K, Munarriz R, Goldstein I . Sex steroid hormones differentially regulate nitric oxide synthase and arginase activities in the proximal and distal rabbit vagina. Int J Impot Res 2003; 15: 397–404.

    Article  CAS  Google Scholar 

  21. Kennedy TG, Armstrong DT . Induction of vaginal mucification in rats with testosterone and17betahydroxy-5alpha-androstan-3-one. Steroids 1976; 27: 423–430.

    Article  CAS  Google Scholar 

  22. Traish AM, Botchevar E, Kim NN . Biochemical factors modulating female genital sexual arousal physiology. J Sex Med 2010; 7: 2925–2946.

    Article  CAS  Google Scholar 

  23. Ruizeveld de Winter JA, Trapman J, Vermey M, Mulder E, Zegers ND, van der Kwast TH . Androgen receptor expression in human tissues: an immunohistochemical study. J Histochem Cytochem 1991; 39: 927–936.

    Article  CAS  Google Scholar 

  24. Wiren KM, Zhang X, Chang C, Keenan E, Orwoll ES . Transcriptional up-regulation of the human androgen receptor by androgen in bone cells. Endocrinology 1997; 138: 2291–2300.

    Article  CAS  Google Scholar 

  25. Takeuchi M, Kakushi H, Tohkin M . Androgens directly stimulate mineralization and increase androgen receptors in human osteoblast-like osteosarcoma cells. Biochem Biophys Res Commun 1994; 204: 905–911.

    Article  CAS  Google Scholar 

  26. Perrone AM, Cerpolini S, Maria Salfi NC, Ceccarelli C, De Giorgi LB, Formelli G et al. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J Sex Med 2009; 6: 3193–3200.

    Article  CAS  Google Scholar 

  27. Rothman MS, Carlson NE, Xu M, Wang C, Swerdloff R, Lee P et al. Re-examination of testosterone, dihydrotestosterone, estradiol and estrone levels across the menstrual cycle and in postmenopausal women measured by liquid chromatography-tandem mass spectrometry. Steroids 2011; 76: 177–182.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Support for this study was provided by grant from the University of Bologna, Bologna, Italy. We thank Pasquale Chieco for statistical assistance and Julie Norbury for language editing.

Author information

Authors and Affiliations

  1. Center for Applied Biomedical Research (CRBA), Alma Mater Studiorum University of Bologna, Bologna, Italy

    M Baldassarre & F A Giannone

  2. S. Orsola–Malpighi University Hospital – NHS Trust, Bologna, Italy

    M Baldassarre, A M Perrone, F Armillotta, C Battaglia, A Costantino, S Venturoli & M C Meriggiola

  3. Department of Clinical Medicine, Alma Mater Studiorum University of Bologna, Bologna, Italy

    M Baldassarre & F A Giannone

  4. Center for protection of Sexual Health, Physiopathology of Reproduction and Gynaecology, Bologna, Italy

    A M Perrone, F Armillotta, C Battaglia, A Costantino, S Venturoli & M C Meriggiola

Authors
  1. M Baldassarre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A M Perrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F A Giannone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F Armillotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Battaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Costantino
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Venturoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M C Meriggiola
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M C Meriggiola.

Ethics declarations

Competing interests

All authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baldassarre, M., Perrone, A., Giannone, F. et al. Androgen receptor expression in the human vagina under different physiological and treatment conditions. Int J Impot Res 25, 7–11 (2013). https://doi.org/10.1038/ijir.2012.25

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijir.2012.25

Keywords

This article is cited by

Search

Advanced search

Quick links