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| Vibrance Newsletter | ||
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| Androgen Receptor Expression in Women and its Relationship to Sexual Function |
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| Written by Jennifer Berman, MD | |||||||||||||
Page 6 of 11 H. Androgen receptor expression in vaginal tissue Although androgens influence clitoral, labial and vaginal physiology, its role in female sexual function is controversial and poorly understood. There is limited biochemical and physiological data on the role of androgens in regulating female genital tissue structure and in modulating female genital sexual response. However, improved libido and orgasmic response as well as increased sexual satisfaction have been reported in women undergoing androgen therapy to alleviate menopausal symptoms. Hemodynamic events during genital sexual arousal are regulated by estrogens and enhanced by androgen supplementation.33, 47 Furthermore, genital sexual arousal in women which is characterized by an increase in genital blood flow, leads to vasocongestion of the vagina, vulva and clitoris, and increased genital sensation, vaginal lengthening and lubrication;3 while changes in the hormonal milieu can alter these physiological processes. Vaginal lubrication is a combination of basal mucin production and vaginal vascular transudate, which constitutes the major estrogen-dependent lubrication component during genital arousal;3 while mucin production and proliferation of vaginal epithelial cells are regulated by androgens.48, 49 The immunohistochemical detection of androgen and estrogen receptors in vaginal tissues has been reported.50 In animal models, the labia majora, labia minora, and vagina stain positive for the androgen receptor and vaginal epithelium responds to T replacement in a similar manner to estrogen replacement, even in the absence of estrogen.51 Although ARs are present in the human vagina, it is unclear whether T acts directly on the receptor or by conversion to DHT or aromatization to estrogen. The enzymes necessary for metabolism of T, aromatase and 5-α reductase, have been found to be expressed in the human vagina, which suggests that they play a role in the conversion of T to DHT and estrogen in the vagina. The presence of aromatase mRNA indicates that some of the effects of T in the vagina are also mediated through conversion to E. In E-depleted women, this residual source of E could be beneficial. Varying levels of aromatase in the vagina may help to explain why postmenopausal women receiving hormone therapy present with different degrees of vaginal maturation and atrophy, sometimes requiring the addition of topical E therapy.51 Berman et al51 confirmed the presence of ARs, mediating both T and DHT actions, in the human vagina, with their density affected by age, menopausal status, and E replacement. Postmenopausal women receiving oral or transdermal E replacement had lower vaginal androgen receptor densities than those who were not. This suggests that E replacement may down-regulate vaginal ARs. Fewer ARs in vaginal subepithelium of women on hormone therapy may results from estrogenic stimulation of sex hormone-binding globulin (SHBG), leading to less free T and therefore, less production of ARs.51 Furthermore, the current study revealed that androgen density is lower in the mucosa of postmenopausal women, irrespective of type or route of hormone therapy. Hence a reduction of androgen receptors in postmenopausal women combined with a gradual age-related decline in serum androgen levels in women may further decrease the androgen responsiveness of vaginal tissue. Nitric Oxide (NO), vasoactive intestinal peptide (VIP), and serotonin are among several biochemical factors implicated in the signaling pathway of genital smooth muscle relaxation. Nitric oxide, which is a product of the conversion of arginine by nitric oxide synthase, has been recognized as an important molecule with a broad range of functions in the lower urinary tract and vagina. Estrogens may affect smooth muscle cell growth in the vagina and the clitoris as well as regulate connective tissue metabolism and nitric oxide synthesis, which may be important in maintaining the functional integrity of vaginal and clitoral smooth muscle function.3 Thickness, rugae of the vaginal wall, and vaginal lubrication have been shown to be estrogen dependent as estrogen deficiency results in thin vaginal walls which are more susceptible to trauma, impaired healing and a less acidic environment predisposed to infection. Vaginal epithelium of ovariectomized mice treated with T or aromatase inhibitors demonstrate an increased number of layers, thickness, and mitotic rates compared to controls.51 In addition, estrogen replacement therapy has been shown to increase pelvic blood flow in menopausal women and in women with surgical or medical oophorectomy.36 |
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| Last Updated ( Monday, 26 March 2007 ) | |||||||||||||
