INFLUENCE OF ESTRADIOL ON THE SPHINGOSINE-1- PHOSPHATE (S1P) SIGNALING PATHWAY IN THE VAGINA

Abstract

1373 INFLUENCE OF ESTRADIOL ON THE SPHINGOSINE-1PHOSPHATE (S1P) SIGNALING PATHWAY IN THE VAGINA Sarah Collins, Rowena Chua, Nirmala Kanika, Moses Tar, Katherine Sandhu, Arnold Melman, Michael E DiSanto*. Bronx, NY. INTRODUCTION AND OBJECTIVE: The vaginal walls help to maintain the bladder in its correct anatomical position preventing pelvic organ prolapse with vaginal smooth muscle (SM) content/tone suggested to play a role. The bioactive lipid S1P is emerging as a master regulator of SM phenotype. S1P interacts with three G-protein-coupled receptors termed S1P1, S1P2 and S1P3 which activate a myriad of signal transduction pathways including the RhoA/Rho-kinase pathway. S1P is present in serum at levels (~1 μM) consistent with SM contraction. The goal of this study was to determine if 1) the major components of the S1P pathway exist in the vagina, 2) regional differences exist in the S1P pathway between distal and proximal vagina, 3) the S1P synthesis pathway is hormonally regulated and 4) S1P serum levels can be used as a noninvasive biomarker of vaginal SM phenotype. METHODS: Vaginal tissue from 6 normal 12 wk female Sprague Dawley rats was divided into the distal one-third and proximal two-thirds and used for regional expression studies. In addition, 3 groups of 8 rats each (sham-operated or bilateral ovariectomy (OVX) for 6 weeks followed by placebo or estradiol (E) pellet for 4 weeks) were generated,