Effect of testosterone on vaginal function in an experimental rat model
Corno, C1; Filippi, S2; Cellai, I1; Comeglio, P1; Corcetto, F1; Maneschi, E1; Maseroli, E1; Maggi, M1; Vignozzi, L1
1: Sexual Medicine and Andrology Unit, Department of Biomedical, Experimental and Clinical Science, University of Florence, Florence, Italy; 2: Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Neuroscience, Drug Research and Child Care, University of Florence, Florence, Italy
Objective: Psychological, neurologic, vascular mechanisms and hormonal factors interact in the female sexual response, which is therefore a complex phenomenon. An increase in genital blood flow is observed during sexual arousal, inducing engorgement of clitoris and lubrication of vagina. In this process the regulation of vascular and non-vascular smooth muscle contraction and relaxation is a crucial step. In a previous study we demonstrated that testosterone (T) and 17β estradiol (17βE2) are both necessary to regulate, respectively, the machinery of pro-erectile/relaxant and anti-erectile/contractile response within the clitoris. They act modulating the nitric oxide (NO) pathway and ras homolog gene family member A (RhoA) / Rho-associated protein kinase (ROCK) pathway. The aim of this study was to investigate how sexual hormones affect in the vagina the previously analyzed molecular pathways.
Material and methods: Female rats were ovariectomized and were treated with 17βE2, progesterone (P), T or T+ letrozole (T+L) for 6 weeks. Intact female rats were taken as control. After sacrifice, harvested vagina samples were cut in two parts, proximal and distal, according to proximity to the uterus.
Results: In distal vagina, ovariectomy (OVX) down-regulated the expression of genes related to the NO-dependent relaxation pathway (endothelial NO synthase, eNOS; guanylate cyclase soluble subunit- β3, GC1β3; cGMP-dependent protein kinase 1, PKG1; phosphodiesterase type 5, PDE5), as well as the contractile pathway genes (RhoA, ROCK1 and ROCK2). This effect was completely counteracted by T and T+L. The contractile pathway was also normalized by 17βE2. T also normalized the smooth muscle marker αSMA (alpha smooth muscle actin), which was down-regulated by OVX.
Conclusions: In conclusion, we observed that 17βE2 acted only on the contractile pathway and treatment with P did not have any effect. Conversely, T showed an important effect on both relaxant and contractile pathways in distal vagina. Co-treatment with L, which inhibits the conversion of T to 17βE2, confirmed these observations. These data suggest that testosterone modulated the relaxation and contractility of vagina smooth muscle cells, therefore promoting a proper sexual activity.
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