BASIC AND TRANSLATIONAL UROLOGY

Oestrogen receptor expression and neuronal nitric oxide synthase in the clitoris and preputial gland structures of mice
Martin-Alguacil N, Schober J, Kow LM, Pfaff D
Department of Neurobiology and Behaviour, The Rockefeller University, New York, NY, USA
BJU Int. 2008; 102: 1719-23

• Objective: To study the presence of oestrogen receptors (ER) and neuronal nitric oxide synthase (nNOS) in the mouse clitoris.
• Materials and Methods: A series of sections of the pelvic area, including the preputial glands and clitoris, of 10 mice were assessed by immunocytochemical studies specific for ER-alpha and -beta, and nNOS; selected sections were also stained with Masson’s trichrome.
• Results: ER alpha was detected in the epithelium of the gland of the clitoris, and in the glandular tissue, preputial and apocrine gland. ER alpha was detected in the nuclei of stromal cells around the cavernous tissue and near the epithelium of the clitoris. Cytoplasm ER alpha was detected in a few cells in an area ventral to the clitoral gland. There was also nuclear staining in the connective tissue cells surrounding the clitoris. Very light ER beta immunostaining was detected in the clitoris and in the tissue related to it. There were some cells with nuclear staining in the vessels of the cavernous tissue of the clitoris. nNOS immunostaining was detected in the clitoris, the preputial gland and the connective tissue.
• Conclusion: ER alpha and beta isoforms, and nNOS, are present in the clitoris and preputial glands of female mice in different cellular locations and with differing levels of receptivity. Functional studies would further elucidate the role of receptor functions and their relationship to the neuronal expression of NO.
  
  
• Editorial Comment
  The authors are to be commended for this interesting study, which provided additional knowledge on the presence of estrogen receptors alpha (ERα) and beta (ß), as well as on neuronal nitric oxide synthase (nNOS) and their relationships, in the mouse clitoris.
  It was found a diffuse and deep immunostaining for ERα in the epithelium of the gland of the clitoris, and in the glandular tissue and prepuce. Also, ERa was detected in the nuclei of stromal cells around the cavernous tissue and near the epithelium of the clitoris. On the other hand, the authors found very few ERß immunostaining in the clitoris and in the tissue related to it. However, there were some cells with nuclear staining in the vessels of the cavernous tissue of the clitoris.
  In a similar pattern of ERα, although not too strong, nNOS immunostaining was detected in the clitoris, the preputial gland and connective tissue.
  Concerning the epithelium of the vaginal wall, it was negative for the immunostaining for ERα and ß. Membrane-based nNOS was found in the vaginal wall, and not along the upper vaginal wall, but only in one part, closest to the vaginal opening.
  The authors proposed that the nuclear immunostaining for ERα in the stroma of the clitoris suggests a higher receptivity to this hormone. All receptors identified in the clitoris tended to be more intensely expressed in stromal than epithelial cells, suggesting that there is a stromal - epithelial interaction induced by the different sex steroids. ERß immunostaining was only detected in a few cells in the vascular lumen of the cavernous tissue of the clitoris.
  By contrast, with ERα, the study showed that there was no staining in the glandular tissue, epithelium or stroma of the clitoris. The authors speculate that these results suggest that ERß is not essential for the normal functions that take place in the clitoris of the mouse.
  nNOS was immunodetected with a similar pattern of distribution to that of ERα. Therefore, the authors proposed that NO might play a role in controlling blood flow and capillary permeability, the mechanisms of sexual lubrication due to cGMP action, induced by NO. The homeostasis of this system needs cGMP breakdown. It is possible that the physiological response to sexual arousal in the female follows the same biochemical pathway as in the male.
  The new knowledge presented in this work, concerning the relationship of estrogen receptivity in the genital sensory field and clitoral vasculogenic processes, represent and important advance in the understanding of the presence and anatomical location of nNOS and ER isoforms.

Dr. Francisco J. B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, RJ, Brazil
E-mail: sampaio@urogenitalresearch.org