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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 8 of 11 In human studies, the expression of AR in levator ani muscle and its fascia has been shown. Copas et al demonstrated the expression of androgen and progesterone receptors in the striated muscle fibers, stromal cells and fascia of levator ani. Estrogen receptors were also present in the stromal cells and fascia of the levator ani, but not in the muscle fibers.58 Ewies et al compared the expression of androgen receptors in human cardinal ligaments of prolapsed uteri with non-prolapsed controls59 and demonstrated that the cardinal ligaments of women with uterine prolapse expressed three to four times more androgen receptors than women without prolapse, implying that androgens may play a role in pelvic organ prolapse.Androgens may also play a role in stress urinary incontinence as urinary levels of androgens have been demonstrated to be significantly higher in postmenopausal patients with stress urinary incontinence compared to postmenopausal women without incontinence. Concentrations of androgen metabolites in the urine of patients with incontinence were positively related to bladder neck descencus as measured by perineal ultrasound.60 J. Androgen receptor expression in endometrial cancer Androgens are aromatized to estrogens in several tissues, including the endometrium. During menopause, extraglandular production of estrogens may play a role in the development of certain forms of endometrial carcinoma that depend on estrogenic stimulation for their growth. Therefore, local intra-tumor aromatization of androgens may play a critical role in stimulating the growth of estrogen-dependent endometrial carcinomas. Maia et al demonstrated immunohistochemical presence of AR in the stroma of non-malignant endometrium which is in accordance with previous studies indicating that the levels of mRNA transcripts for AR are much higher in the endometrial stromal cells than in the glandular epithelium.61 However in endometrioid endometrial adenocarcinoma, there is a shift of AR towards the malignant epithelium with little staining of the intervening stroma, which may suggest a role for the AR in the mechanism of cellular growth in estrogen-dependent endometrial carcinomas. Previous studies have shown that the stimulatory effects of testosterone on the growth of certain cell lines of endometrial carcinoma in vitro were only observed in tumors that were capable of responding to estrogens.62 This stimulatory effect was dependent on the presence of an aromatase enzymatic system capable of converting androgens into estrogens. Thus intra-tumor aromatization of androgen precursors may therefore generate a hyper-estrogenic milieu in the carcinoma, stimulating tumor growth during menopause despite the presence of low plasma levels of estrogens. Consequently during menopause, as most estrogens originate from the extraglandular conversion of androgen precursors, patients with estrogen-dependent endometrial carcinoma will demonstrate strong immunohistochemical staining for testosterone receptors in the glandular epithelium.61 K. Androgen receptor expression in ovarian cancer Epidemiological evidence supports the possibility of an androgen-ovarian cancer link as most ovarian cancers express AR, and antiandrogens inhibit ovarian cancer growth.12 Oral contraceptives, the most effective chemoprotective agent against ovarian cancer, suppress ovarian testosterone production by 35-70%.12 In contrast, there is evidence that the AR gene may have an ovarian tumor suppressor function. Androgen receptor mRNA and protein are down-regulated in ovarian cancer. Furthermore, loss of heterozygosity in the region containing the gene has been reported in approximately 40% of ovarian cancers. In addition, nonrandom X-inactivation has been reported in invasive ovarian cancer, with expression potentially favoring the allele producing the less active receptor protein.12 While androgens, acting through AR have been implicated in the disease, progestins, acting through progesterone receptors, may provide protection against the disease. Based on mounting evidence in support of the role of androgens and progestins in ovarian cancer, polymorphisms in the androgen and progesterone receptor genes may act as risk factors for ovarian cancer and/or as modifiers of risk associated with exposure to hormonal factors including oral contraceptive use, parity, and BRCA 1/2 mutation status.12 Future studies across large, diverse populations are necessary to identify more precisely the contribution of genetic factors and/or environmental exposures to the etiology of ovarian cancer. |
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| Last Updated ( Monday, 26 March 2007 ) | |||||||||||||
