madman
Super Moderator
Expression of androgen receptors in the structures of vulvovaginal tissue
Santiago Palacios, MD
Abstract
Importance and Objective: Little is known about the role of androgens in the female genital tract, specifically in the vulvovaginal area. The abundance of androgen receptors in this area could help us to explain their role. The main objective of the present article is to review current data on androgen receptors in the different structures of vulvovaginal tissues.
Methods: A review of the literature using data from PubMed was carried out on androgen receptors in the vulva, labia majora and minora, vestibule, clitoris, and vagina. The effects of androgens and regulation of androgen receptors both in the embryo and in premenopausal and postmenopausal women were also reviewed. Given the characteristics of this review, we also analyzed animal studies and animal models of human disease. There were no filters or restrictions with respect to the date of publication.
Discussion: Androgen receptors have been detected throughout the genitourinary tract by means of Western blot, immunohistochemistry, ligand binding, and gene expression. They are present in the labia majora and minora, the clitoris, the vestibule, and in the three layers of the vaginal mucosa (epithelium, lamina propria, and muscularis). More specifically, studies on the labia majora have shown that androgen receptors seem to be particularly abundant in epidermal keratinocytes and in dermal fibroblasts. Androgen receptors are also abundant in the epidermis, especially in the keratinocytes, and in the dermis of the labia minora and vestibule, where they are more numerous than in the vagina. Androgen receptors have also been found in the Bartholin glands.
Conclusions: Estrogens play a major role in the maintenance of vaginal physiology. Although little is known about the role of androgens in the genital apparatus of women, specifically in the vulvovaginal area, the abundance of androgen receptors could enable us to explain their role. Androgens and estrogens play a major role in the maintenance of vaginal physiology. Better knowledge of the role of androgens and their receptors in vulvovaginal tissue would make it possible to discern their effects on female genitalia and help us to understand new therapeutic strategies.
Hormones have an effect on the growth, development, differentiation, and sensitivity of the genitals. Studies on the action of hormones and their receptors suggest that female phenotypic differentiation of the external genitals is an active process that depends on both estrogens and androgens.1,2 Furthermore, androgens and estrogens are essential physiological modulators in the maintenance of the structure and function of genital tissue.3,4 The effects of estrogens on the genital apparatus are well known, as are the changes associated with their decrease during menopause.5 Various studies have demonstrated the presence of estrogen receptors (ERs) on the vaginal walls, labia minora, vestibule, clitoris, and—albeit to a lesser extent—labia majora.2,6
In the labia majora, which are composed of skin, ERs have been found in luminal epithelial cells in the apocrine sweat glands and in dermal fibroblasts in the skin. They have, however, not been observed in the blood vessels of the skin or in the lymphatic system.2 ERs are found in the epidermis and dermis of the labia minora,2 as well as in the corpus cavernosum and smooth muscle of the clitoris, and are abundant in the three layers of the vaginal mucosa (epithelium, lamina propria [fibroblasts], and muscularis).2 ERa is distributed in both the epithelium and in the stroma, with greater density in the parabasal cells. The cellular distribution of ERb is similar to that of ERa, although ERb are not as abundant or prominent.7
Women have a greater amount of androgens than estrogens both during reproductive life and in the postmenopausal period.8,9 Although little is known about the role of androgens in the genital apparatus of women, specifically in the vulvovaginal area,10 the abundance of androgen receptors (ARs) could enable us to explain their role.2,11 In fact, androgens contribute to the maintenance of the structure and function of genitourinary tissue. The effects of androgens may differ from those of estrogens or may complement the action of estrogens. The processes mediated by androgens may be involved in total or partial resolution of the genitourinary syndrome in menopausal women.10 Better knowledge of the role of androgens and ARs in vulvovaginal tissue would make it possible to discern their effects on the female genitalia and help us to understand new therapeutic strategies.
*Labia majora
*Clitoris and vestibular bulbs
*Labia minora
*Vestibule
*Vagina
CONCLUSION
Our data indicate that ARs can play an important role in the vulvovaginal area. Although the number of ERs seems to be greater in the vagina, the number of ARs is greater in the vestibule, labia minora, and labia majora.
The role of estrogens at the vulvovaginal level is well known, with increased superficial cells, reduced basal cells, decreased pH, and improvement in the main symptoms, such as dryness and dyspareunia.57 Little is known about the role of androgens at the vulvovaginal level. The large amount of ARs in the vestibule and labia majora and minora lead us to consider a possible role of androgens in local immunity and inflammatory processes. Thus, the biological function of epidermal ARs in the labia majora may be necessary for specialized differential functions of the keratinocytes. In addition to their structural function, epidermal keratinocytes play a key role in the immune and inflammatory response of the skin.58,59
Furthermore, the high number of ARs in the clitoris points to a possible role in increasing the sensitivity of the clitoris and in sexual functioning.34,36,38 In women who received long-term treatment with testosterone (intramuscular Testoviron depot 100 mg every 7-10 days for 1 year) before surgery, expression of the mRNA of ARs was significantly greater in the vaginal tissue than in postmenopausal women.11 Similarly, ovariectomy in rats downregulated expression of ARs, and testosterone replacement restored AR expression in the vagina.24 Immunohistochemistry also demonstrated a greater density of ARs in the muscle layer of the vagina of ovariectomized rats who received testosterone supplementation.25 Therefore, circulating testosterone is positively correlated with the expression of ARs in the vagina.
*Demonstration of the presence of ARs in the various areas of the vulva and vagina indicates that androgens are likely necessary for maintaining the physiology and morphology of tissue in the vagina, vestibule, clitoris, and labia minora and majora. This concept should be further investigated to establish the precise role of androgens in this context.
Santiago Palacios, MD
Abstract
Importance and Objective: Little is known about the role of androgens in the female genital tract, specifically in the vulvovaginal area. The abundance of androgen receptors in this area could help us to explain their role. The main objective of the present article is to review current data on androgen receptors in the different structures of vulvovaginal tissues.
Methods: A review of the literature using data from PubMed was carried out on androgen receptors in the vulva, labia majora and minora, vestibule, clitoris, and vagina. The effects of androgens and regulation of androgen receptors both in the embryo and in premenopausal and postmenopausal women were also reviewed. Given the characteristics of this review, we also analyzed animal studies and animal models of human disease. There were no filters or restrictions with respect to the date of publication.
Discussion: Androgen receptors have been detected throughout the genitourinary tract by means of Western blot, immunohistochemistry, ligand binding, and gene expression. They are present in the labia majora and minora, the clitoris, the vestibule, and in the three layers of the vaginal mucosa (epithelium, lamina propria, and muscularis). More specifically, studies on the labia majora have shown that androgen receptors seem to be particularly abundant in epidermal keratinocytes and in dermal fibroblasts. Androgen receptors are also abundant in the epidermis, especially in the keratinocytes, and in the dermis of the labia minora and vestibule, where they are more numerous than in the vagina. Androgen receptors have also been found in the Bartholin glands.
Conclusions: Estrogens play a major role in the maintenance of vaginal physiology. Although little is known about the role of androgens in the genital apparatus of women, specifically in the vulvovaginal area, the abundance of androgen receptors could enable us to explain their role. Androgens and estrogens play a major role in the maintenance of vaginal physiology. Better knowledge of the role of androgens and their receptors in vulvovaginal tissue would make it possible to discern their effects on female genitalia and help us to understand new therapeutic strategies.
Hormones have an effect on the growth, development, differentiation, and sensitivity of the genitals. Studies on the action of hormones and their receptors suggest that female phenotypic differentiation of the external genitals is an active process that depends on both estrogens and androgens.1,2 Furthermore, androgens and estrogens are essential physiological modulators in the maintenance of the structure and function of genital tissue.3,4 The effects of estrogens on the genital apparatus are well known, as are the changes associated with their decrease during menopause.5 Various studies have demonstrated the presence of estrogen receptors (ERs) on the vaginal walls, labia minora, vestibule, clitoris, and—albeit to a lesser extent—labia majora.2,6
In the labia majora, which are composed of skin, ERs have been found in luminal epithelial cells in the apocrine sweat glands and in dermal fibroblasts in the skin. They have, however, not been observed in the blood vessels of the skin or in the lymphatic system.2 ERs are found in the epidermis and dermis of the labia minora,2 as well as in the corpus cavernosum and smooth muscle of the clitoris, and are abundant in the three layers of the vaginal mucosa (epithelium, lamina propria [fibroblasts], and muscularis).2 ERa is distributed in both the epithelium and in the stroma, with greater density in the parabasal cells. The cellular distribution of ERb is similar to that of ERa, although ERb are not as abundant or prominent.7
Women have a greater amount of androgens than estrogens both during reproductive life and in the postmenopausal period.8,9 Although little is known about the role of androgens in the genital apparatus of women, specifically in the vulvovaginal area,10 the abundance of androgen receptors (ARs) could enable us to explain their role.2,11 In fact, androgens contribute to the maintenance of the structure and function of genitourinary tissue. The effects of androgens may differ from those of estrogens or may complement the action of estrogens. The processes mediated by androgens may be involved in total or partial resolution of the genitourinary syndrome in menopausal women.10 Better knowledge of the role of androgens and ARs in vulvovaginal tissue would make it possible to discern their effects on the female genitalia and help us to understand new therapeutic strategies.
*Labia majora
*Clitoris and vestibular bulbs
*Labia minora
*Vestibule
*Vagina
CONCLUSION
Our data indicate that ARs can play an important role in the vulvovaginal area. Although the number of ERs seems to be greater in the vagina, the number of ARs is greater in the vestibule, labia minora, and labia majora.
The role of estrogens at the vulvovaginal level is well known, with increased superficial cells, reduced basal cells, decreased pH, and improvement in the main symptoms, such as dryness and dyspareunia.57 Little is known about the role of androgens at the vulvovaginal level. The large amount of ARs in the vestibule and labia majora and minora lead us to consider a possible role of androgens in local immunity and inflammatory processes. Thus, the biological function of epidermal ARs in the labia majora may be necessary for specialized differential functions of the keratinocytes. In addition to their structural function, epidermal keratinocytes play a key role in the immune and inflammatory response of the skin.58,59
Furthermore, the high number of ARs in the clitoris points to a possible role in increasing the sensitivity of the clitoris and in sexual functioning.34,36,38 In women who received long-term treatment with testosterone (intramuscular Testoviron depot 100 mg every 7-10 days for 1 year) before surgery, expression of the mRNA of ARs was significantly greater in the vaginal tissue than in postmenopausal women.11 Similarly, ovariectomy in rats downregulated expression of ARs, and testosterone replacement restored AR expression in the vagina.24 Immunohistochemistry also demonstrated a greater density of ARs in the muscle layer of the vagina of ovariectomized rats who received testosterone supplementation.25 Therefore, circulating testosterone is positively correlated with the expression of ARs in the vagina.
*Demonstration of the presence of ARs in the various areas of the vulva and vagina indicates that androgens are likely necessary for maintaining the physiology and morphology of tissue in the vagina, vestibule, clitoris, and labia minora and majora. This concept should be further investigated to establish the precise role of androgens in this context.
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