FEMALE SEXUAL AROUSAL: CLITORAL AND VAGINAL PHYSIOLOGY
Principal Investigator: Abdulamaged M Traish
Abstract: DESCRIPTION (Adapted from the Applicant's Abstract): Female sexuality is an desire, arousal, orgasm or pain, are estimated to afflict 30-50 percent of women in the United States. These disorders may be chronic, progressive, age-related and adversely affect quality of life and interpersonal relationships. In particular, sexual arousal disorder, has been linked to age, menopause, hysterectomy and vascular risk factors. Overall clinical management of afflicted patients has been primarily psychologically and hormonally-based. There has been limited research attention to the physiologically or medically-based conditions which adversely affect the female sexual arousal response. Recently, increasing numbers of afflicted women are utilizing "off-label" oral vasoactive agents for treatment of diminished genital swelling/lubrication responses in the absence of such physiologic and clinical trial data, suggesting demand for improved female sexual health care management. There is a need to broaden understanding of the pathophysiologic mechanisms of female sexual dysfunction. The overall goal of this proposal is to define the physiological mechanisms underlying the arousal component of the female sexual response. Specifically, they will investigate the physiologic mechanisms of clitoral and vaginal smooth muscle contractility which contribute to clitoral and vaginal engorgement during genital swelling/lubrication responses. To accomplish this goal, they have developed several experimental systems including: I) an in vivo animal model to record physiologic and hemodynamic changes in the clitoris and vagina following pelvic nerve stimulation, ii) in vitro organ baths of clitoral and vaginal tissue to investigate mechanisms involved in the modulation of smooth muscle contractility and iii) primary cultures of human and animal clitoral and vaginal smooth muscle cells to examine signal transduction pathways underlying smooth muscle tone. The Specific Aims of this proposal are to investigate: 1) neurogenic mechanisms modulating clitoral and vaginal smooth muscle contractility, 2) signal transduction pathways by which alpha-adrenergic receptors, nitric oxide and VIP modulate smooth muscle function, 3) the activity, in vivo, of alpha-adrenergic antagonists, VIP and nitric oxide on clitoral and vaginal hemodynamic response to pelvic nerve stimulation and 4) the role of estrogens in modulating vaginal and clitoral smooth muscle function. These studies should lead to new and useful information concerning physiological and pathophysiological mechanisms in female sexual arousal and to potentially improve diagnostic and treatment strategies for women suffering from sexual dysfunction.
Funding Period: 2000-09-15 - 2005-06-30
more information: NIH RePORT
- Weapons of penile smooth muscle destruction: androgen deficiency promotes accumulation of adipocytes in the corpus cavernosumA M Traish
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Aging Male 8:141-6. 2005..Androgen deficiency promotes differentiation into adipogenic lineage, and accumulation of adipocytes in the corpus cavernosum may contribute to erectile dysfunction...
- Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunctionAbdulmaged M Traish
Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
Eur Urol 52:54-70. 2007....
- Adipocyte accumulation in penile corpus cavernosum of the orchiectomized rabbit: a potential mechanism for veno-occlusive dysfunction in androgen deficiencyAbdulmaged M Traish
Department of Biochemistry, Institute for Sexual Medicine, Boston University School of Medicine, 700 Albany St, Room W607, Boston, MA 02118, USA
J Androl 26:242-8. 2005..We hypothesize that androgen deprivation promotes differentiation of progenitor stroma cells into an adipogenic lineage producing fat-containing cells, thus altering erectile function...
- Differential effects of estradiol, progesterone, and testosterone on vaginal structural integrityMonica A Pessina
Department of Anatomy and Neurobiology, Institute for Sexual Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Endocrinology 147:61-9. 2006..Present observations also suggest that combined replacement regimens may be required for an optimal physiological response...
- Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidenceAbdulmaged M Traish
Department of Biochemistry and Urology, Institute for Sexual Medicine, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA, USA
J Sex Med 3:382-404; discussion 404-7. 2006..Nevertheless, based on the preclinical and clinical data available in the literature, to date, we infer that androgens play a critical role in maintaining erectile physiology in humans...
- Streptozotocin-induced diabetes in the rat is associated with changes in vaginal hemodynamics, morphology and biochemical markersNoel N Kim
Institute for Sexual Medicine, Department of Urology, Boston University School of Medicine, Boston, USA
BMC Physiol 6:4. 2006..We further related these changes with estrogen receptor alpha (ERalpha) and androgen receptor (AR) expression...
- Differential regulation of the expression of estrogen, progesterone, and androgen receptors by sex steroid hormones in the vagina: immunohistochemical studiesMonica A Pessina
Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA
J Sex Med 3:804-14. 2006..The goal of this study was to assess changes in steroid hormone receptor expression and distribution in response to sex steroid hormone deprivation and administration...