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.

  • Paper
  • Published:

Effects of estrogen on nitric oxide synthase and histological composition in the rabbit clitoris and vagina

International Journal of Impotence Research volume 13, pages 205–211 (2001)Cite this article

Abstract

We investigated the functional and histological changes after oophorectomy in the rabbit clitoris and vagina to determine the mechanism responsible for the development of arousal disorder in postmenopausal women. Twenty mature female New Zealand white rabbits were randomly divided into three groups: control; oophorectomy; and estrogen replacement after oophorectomy. We compared the nitric oxide synthase (NOS) activity and the degree of expression of neuronal (nNOS) and endothelial NOS (eNOS) using biochemical and Western blot analysis in clitoral and vaginal tissues. Histological change of smooth muscle and collagen contents in those tissues were also compared using Masson's trichrome staining. NOS activity and the expression of nNOS and eNOS were significantly increased in the oophorectomized group while there was a decrease to the level of the control group in the estrogen replacement group. Histological examination showed that oophorectomy induced a significant increase in collagen and decrease in muscle content in both clitoris and vagina, while the ratio of smooth muscle content was increased significantly after the estrogen replacement. Our results clearly demonstrate that estrogen deficiency induces compensatory NOS production which may be related to decreases in muscle to collagen ratio in female rabbit genital organs.

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

Similar content being viewed by others

References

  1. Cosentino F, Luscher TF . Nitric oxide and endothelial regulation of vascular tone. In: Maines MD (ed). Nitric Oxide Synthase: Characterization and Functional Analysis Academic Press: London 1996 215–227

    Chapter  Google Scholar 

  2. Zavara P et al.. Nitric oxide mediated erectile activity is a testosterone dependent event: a rat erection model. Int J Impot Res 1995 7, 209–219

    Google Scholar 

  3. Burnett AL et al.. Immunohistochemical description of nitric oxide synthase isoforms in human clitoris. J Urol 1997 158, 75–78

    Article  CAS  Google Scholar 

  4. Malinski T, Eugeniusz K, Kiechle F . Electrochemical and spectroscopic methods of nitric oxide detection. Methods in Neuroscience 1996 31, 14–33

    Article  CAS  Google Scholar 

  5. Bloch W et al.. Evidence for the involvement of endothelial nitric oxide synthase from smooth muscle cells in the erectile function of the human corpus cavernosum. Urol Res 1998 26, 129–135

    Article  CAS  Google Scholar 

  6. Champion HC et al.. Induction of penile erection by intracavernosal and transurethral administration of novel nitric oxide donors in the cat. J Urol 1999 161, 2013–2019

    Article  CAS  Google Scholar 

  7. Raifer J et al.. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. New Engl J Med 1992 326, 90–94

    Article  Google Scholar 

  8. Traish AM et al.. Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 1999 140, 1861–1868

    Article  CAS  Google Scholar 

  9. Grozdanovic Z, Bernd M, Baumagarten H, Bruning G . Nitric-oxide synthase-containing nerve fibers and neurons in the genital tract of the female mouse. Cell Tissue Res 1994 275, 355–360

    Article  CAS  Google Scholar 

  10. Majewski M et al.. The distribution and co-localization of immunoreactivity to nitric oxide synthase, vasoactive intestinal polypeptide and substance P within nerve fibers supplying bovine and porcine genital organs. Cell Tissue Res 1995 281, 445–464

    Article  CAS  Google Scholar 

  11. Dong YL, Gangula PR, Yallampalli C . Nitric oxide synthase isoforms in the rat uterus: differential regulation during pregnancy and labor. J Reprod Fertil 1996 107, 249–254

    Article  CAS  Google Scholar 

  12. Veille JC et al.. Effects of estrogen on nitric oxide biosynthesis and vasorelaxant activity in sheep uterine and renal arteries. Am J Obstet Gynecol 1996 174, 1043–1049

    Article  CAS  Google Scholar 

  13. Bryant CE et al.. Nitric oxide synthase in the rat fallopian tube is regulated during the oestrous cycle. J Endocrinol 1995 146, 149–157

    Article  CAS  Google Scholar 

  14. Goetz RM et al.. Increased expression of endothelial nitric oxide synthase in the rat aorta during pregnancy. Biochem Biophys Res Commun 1994 205, 905–910

    Article  CAS  Google Scholar 

  15. Figueroa JP, Massaman AG . Estrogen increases nitric oxide synthase activity in the uterus of nonpregnant sheep. Am J Obstet Gynecol 1995 173, 1539–1545

    Article  CAS  Google Scholar 

  16. Berman JR et al.. Clinical evaluation of female sexual function: effects of age and estrogen status on subjective and physiologic sexual responses. Int J Impot Res 1999 11, (Suppl 1): S31–S38

    Article  Google Scholar 

  17. Berman JR, McCarthy MM, Kyprianou N . Effect of estrogen withdrawal on nitric oxide synthase expression and apoptosis in the rat vagina. Urology 1998 51, 650–656

    Article  CAS  Google Scholar 

  18. Batra S, Al-Hijji J . Characterization of nitric oxide synthase activity in rabbit uterus and vagina: down regulation by estrogen. Life Sci 1998 62, 2093–2100

    Article  CAS  Google Scholar 

  19. Al-Hijji J, Batra S . Downregulation by estrogen of nitric oxide synthase activity in the female rabbit lower urinary tract. Urology 1999 53, 637–641

    Article  CAS  Google Scholar 

  20. Rosenfeld CR, Cox BE, Roy T, Magness RR . Nitric oxide contributes to estrogen-induced vasodilation of the ovine uterine circulation. J Clin Invest 1996 98, 2158–2166

    Article  CAS  Google Scholar 

  21. Sutherland RS, Kogan BA, Piechota HJ, Bredt DS . Vesicourethral function in mice with genetic disruption of neuronal nitric oxide synthase. J Urol 1997 157, 1109–1116

    Article  CAS  Google Scholar 

  22. Hoyle CH et al.. Innervation of vasulature and microvasculature of the human vagina by NOS and neuropeptide-containing nerves. J Anat 1996 188, 633–644

    PubMed  PubMed Central  Google Scholar 

  23. Hayashi T et al.. Estrogen increases endothelial nitric oxide by a receptor mediated system. Biochem Biophys Res Commun 1995 214, 847–855

    Article  CAS  Google Scholar 

  24. Batra S . Increased by oestrogen of calcium entry and calcium channel density in uterine smooth muscle. Br J Pharmacol 1987 92, 389–392

    Article  CAS  Google Scholar 

  25. Batra S . Influence of chronic oestrogen treatment on the density of muscarinic cholinergic receptors and calcium channels in the rabbit uterus. J Endocrinol 1990 125, 185–189

    Article  CAS  Google Scholar 

  26. Vedernikov YP et al.. Effect of chronic treatment with 17β-estradiol and progesterone on endothelium-dependent and endothelium-independent relaxation in isolated aortic rings from ovariectomized rats. Am J Obstet Gynecol 1997 176, 603–608

    Article  CAS  Google Scholar 

  27. Ehrén I et al.. Induction of calcium dependent nitric oxide synthase by sex hormones in the guinea-pig urinary bladder. Acta Physiol Scand 1995 153, 393–394

    Article  Google Scholar 

  28. Weiner CP et al.. Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA 1994 91, 5212–5216

    Article  CAS  Google Scholar 

  29. Batra S, Sjöberg NO, Thorberg G . Sex steroids in plasma and reproductive organs of the female guinea pig. Biol Reprod 1980 22, 430–437

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by The Korean Research Foundation (grant number F00236).

Author information

Authors and Affiliations

  1. Department of Urology, Medical Research Center, Seoul, Korea

    HN Yoon, WS Chung, YY Park, BS Shim & SW Kwon

  2. Department of Pathology, Ewha Womans University College of Medicine, Seoul, Korea

    WS Han

Authors
  1. HN Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. WS Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. YY Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. BS Shim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. WS Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. SW Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to HN Yoon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoon, H., Chung, W., Park, Y. et al. Effects of estrogen on nitric oxide synthase and histological composition in the rabbit clitoris and vagina. Int J Impot Res 13, 205–211 (2001). https://doi.org/10.1038/sj.ijir.3900687

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijir.3900687

Keywords

This article is cited by

Search

Advanced search

Quick links