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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 7 of 11 The physiologic response in vaginal tissues to androgens is also mediated by specific androgen receptors. These effects may be related to maintenance of nonvascular smooth muscle function in the vagina and of vascular smooth muscle in the clitoris. Traish et al3 characterized androgen expression in proximal and distal vaginal tissues from control and ovariectomized animals treated with or without estrogen and/or androgen replacement therapy. It was demonstrated that androgens enhance nitric oxide synthase expression and activity and down-regulated arginase (a substrate for nitric oxide synthase) activity in the proximal vagina, which may be manifested in facilitation of vaginal smooth muscle relaxation to electric field stimulation and VIP in androgen-treated animals. Estrogens, on the other hand, down-regulate nitric oxide synthase activity and increase arginase activity which may result in attenuation of vaginal tissue relaxation to electric field stimulation and to VIP.3 These observations suggest that androgens play an important role in modulating the physiology of vaginal tissue and may contribute to modulation of the genital sexual response in women.I. Androgen receptor expression in the female pelvic floor and lower urinary tract Disorders of the pelvic floor, including urinary and fecal incontinence as well as pelvic organ prolapse are major health problems for women, as the incidence of these disorders increase with age, particularly in postmenopausal women. Muscles of the pelvic floor and lower urinary tract are involved in the support of the pelvic organs and micturition, and damage to these muscles or lack of hormonal stimulation may cause pelvic organ prolapse and/or urinary incontinence in women. The presence of androgen receptors in levator ani muscle in animal rat models is well documented and have been used widely as a bioassay of androgenic activity.52-54 In fact, higher levels of androgen receptor expression have been found in the levator ani muscle than in other skeletal muscles of the rat. Furthermore, androgen responsiveness depends not only on the androgen receptor expression within the particular muscle, but also on the particular cell type within that muscle55 Androgen receptors have also been found in the urethral and trigonal epithelium, detrusor muscle and smooth muscle of the urethra in rabbits.56 In addition, studies on male rats have demonstrated that androgen receptors and β-estrogen receptors were coexpressed in the urothelium, neurons, bladder smooth muscle cells, and proximal urethra striated muscle cells, suggesting that androgens may play an important role in the regulation of voiding function either by direct effects and/or indirect effects through interaction with estrogen in the lower urinary tract.52, 57 Nnodim demonstrated the marked changes in muscle mass of the levator ani that occurs after castration and T supplementation in rats.53, 54 In the group of denervated levator ani muscle but gonad-intact rats, myofiber cross-sectional area was markedly diminished and satellite cell nuclei increased significantly. In the group of castrated rats, pronounced myofiber atrophy was observed but satellite cells were not affected. The combination of castration and denervation of levator ani produced the same degree of myofiber atrophy as denervation alone but had no impact on the satellite cells. These results demonstrated that removal of androgen source caused an atrophic effect on levator ani in a similar fashion as denervation as well as diminished the muscle’s ability to recruit and proliferate satellite cells. The administration of exogenous T to the castrated adult rats restored the myofiber cross-sectional areas and increased satellite cell proliferation. Hence the anabolic effects of androgen play an important role in the levator ani of rats. |
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| Last Updated ( Monday, 26 March 2007 ) | |||||||||||||
