581 NEUROCHEMICHAL CORRELATIONS OF A MODEL OF MALE SEXUAL BEHAVIOUR IMPAIRMENT INDUCED BY ANTENATAL CORTICOTHERAPY
582 IS THERE A SIGNIFICANCE OF BETA-ENDORPHIN IN THE CONTROL OF THE MALE ERECTILE RESPONSE? Becker A.1, Schröder M.2, Ückert S.2, Scheller F., Jonas U.2, Stief C.1
Oliveira M., Leao P., Sousa N. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Neurosciences Research Domain, Braga, Portugal Introduction & Objectives: Antenatal short-term synthetic corticotherapies are commonly used LQFOLQLFDOSUDFWLFHLQRUGHUWRDFFHOHUDWHOXQJPDWXUDWLRQ5HFHQWFOLQLFDOᚏQGLQJVDQGDQLPDO UHVHDUFKGDWDKDYHHPSKDVL]HGLWVSRWHQWLDOQR[LRXVHᚎHFWVODWHURQOLIHLQFOXGLQJVLJQLᚏFDQW behavioural impairments. An HPA axis permanent disruption seems to play a critical role in these phenomena and other treatments with natural ligands of corticosteroid receptors have been suggested to be less detrimental. Since no prior studies have focused on the potential implications of these short-term prenatal treatments on adult male rat sexual behaviour, we WKRXJKWRILQWHUHVWWRDVVHVVWKHPDQGWRFRPSDUHWKHLPSDFWRIWKHXVHRIGLᚎHUHQWOLJDQGV of corticosteroid receptors. Furthermore, we looked for potential neurochemical correlations of these treatments. Material & Methods: Pregnant Wistar rats were injected with dexamethasone (DEX-1mg/ kg), corticosterone (CORT-25mg/kg) or saline (CONT) on gestational days 18 and 19. Male RᚎVSULQJQ ZKHQDJHGPRQWKVZHUHHYDOXDWHGIRUPDOHVH[XDOEHKDYLRXUE\H[SRVXUH to sexually receptive ovariectomised females. Mounting, intromissions and ejaculations were DVVHVVHG )ROORZLQJ VDFULᚏFH YDULRXV EUDLQ DUHDV ZHUH PLFUR GLVVHFWHG K\SRWKDODPXV VWULDWXP DP\JGDOD DQG EHG QXFOHXV RI VWULD WHUPLQDOLV DQG IUR]HQ 7LVVXH TXDQWLᚏFDWLRQ RI GLᚎHUHQW QHXURWUDQVPLWWHUV GRSDPLQH VHURWRQLQ DQG UHVSHFWLYH PHWDEROLWHV ZDV SHUIRUPHG by high performance liquid chromatography (HPLC). In addition, testis wet weight and serum WHVWRVWHURQHOHYHOVZHUHGHWHUPLQHG'DWDZDVDQDO\]HGXVLQJPXOWLYDULDWH$129$VWDWLVWLFDO VLJQLᚏFDQFHZDVFRQVLGHUHGZKHQS Results: 6LJQLᚏFDQW GHFUHDVH RQ QXPEHU RI PRXQWV DQG LQWURPLVVLRQV ZDV IRXQG RQ '(; exposed, but not on CORT-exposed subjects, which displayed an intermediate sexual behavioural pattern. Also, increased latency time to mounting and intromission was found in the male progeny of DEX-treated dams. Both controls and CORT subjects displayed higher LQWURPLVVLRQ UDWLRV DQ LQGLFDWRU RI HᚑFLHQF\ RI SHQLOH HUHFWLRQ ZKHQ FRPSDUHG WR '(; exposed animals. Reduced serum testosterone levels were also found on DEX progeny. 7HVWLVZHWZHLJKWZDVQRWDᚎHFWHG,QDGGLWLRQGLᚎHUHQFHVZHUHIRXQGRQWKHH[SUHVVLRQRI QHXURWUDQVPLWWHUVLQGLᚎHUHQWEUDLQDUHDV Conclusions: The data we herein present suggest that antenatal dexamethasone impairs male sexual behaviour in adulthood, whilst equipotent corticosterone therapies trigger a less detrimental outcome. These behavioural impairments are correlated with hormonal disruption DQG EUDLQ DUHDV W\SLFDOO\ LPSOLFDWHG LQ VH[XDO EHKDYLRXU VHHP WR EH DᚎHFWHG +RZHYHU DGGLWLRQDOVWXGLHVDUHHVVHQWLDOWRHOXFLGDWHWKHPHFKDQLVPVXQGHUO\LQJWKHVHHᚎHFWV
1 Ludwig-Maximilians-University, Faculty of Medicine, Dept. of Urology, Munich, Germany, 2Hanover Medical School, Dept. of Urology, Hanover, Germany, Hanover Medical School, Dept. of Nuclear Medicine, Hanover, Germany
Introduction & Objectives: Beta (ß)-Endorphin, a member of the family of endogenous QHXURSHSWLGHV LV DQ RSLRLG SHSWLGH FRPSRVHG RI DPLQR DFLGV $OWKRXJK LW KDV been speculated that ß-Endorphin might facilitate the inhibition of the male sexual response including penile erection and seminal emission, its role and function in the control of the penile erectile tissue (Corpus cavernosum penis) is only poorly understood. The aim of our study was to evaluate the course of ß-Endorphin plasma OHYHOVWKURXJKGLᚎHUHQWVWDJHVRIVH[XDODURXVDOLQWKHV\VWHPLFDQGFDYHUQRXVEORRG of healthy male subjects. Material & Methods: 7KLUW\ KHDOWK\DGXOWPDOHVDJHGWR\HDUVPHDQDJH 26 years) were exposed to erotic stimuli in order to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum (CC) and a FXELWDOYHLQ&9 GXULQJWKHSHQLOHFRQGLWLRQVᚐDFFLGLW\) Q WXPHVFHQFH (T) (n = 25/28), rigidity (R) (n = 29/27), and detumescence (D) (n = 18/27). Plasma levels of ß-Endorphin (pmol/L) were determined by means of a radioimmunoassay 5,$ 7KH HᚎHFWV RI ¡(QGRUSKLQ RQ WKH WHQVLRQ RI LVRODWHG KXPDQ SHQLOH HUHFWLOH tissue were evaluated using the organ bath technique. Results: ß-Endorphin in concentrations from 1 pmol - 1 µM did neither induce a VLJQLᚏFDQWFRQWUDFWLOHUHVSRQVHRIWKHFDYHUQRXVWLVVXHQRUUHYHUVHWKHFRQWUDFWLRQ induced by nor epinephrine (Rmax = 24%). Mean ß-Endorphin plasma levels in the V\VWHPLFFLUFXODWLRQGHFUHDVHGZLWKWKHEHJLQQLQJRIVH[XDODURXVDOZKHQWKHᚐDFFLG SHQLVEHFDPHWXPHVFHQWDQGULJLG) SPRO/7 SPRO/5 SPRO/ DQG DJDLQLQFUHDVHGLQWKHSKDVHRIGHWXPHVFHQFH' SPRO/ ,QWKHFDYHUQRXV blood (CC), no alterations in ß-Endorphin plasma concentrations were observed. Conclusions: Our results are not in support for a direct action of ß-Endorphin on the penile erectile tissue. Nevertheless, the drop in ß-Endorphin observed in the systemic EORRGGXULQJWKHSKDVHVRI7DQG5PD\UHᚐHFWWKHLQKLELWLRQRIWKHRSLRLGHUJLFLQSXW with the beginning of sexual arousal.
583 HYDROGEN SULPHIDE AS A MEDIATOR OF PENILE ERECTION Mirone V., D’Emmanuele Di Villabianca R., Sorrentino R., Fusco F., Longo N., Verze P., Buonopane R., Cirino G.
584 THE INTERACTION BETWEEN ANGIOTENSIN II AND NITRIC OXIDE ON RABBIT CORPUS CAVERNOSAL SMOOTH MUSCLE FUNCTION Ertemi H.1, Lau D.1, Mumtaz F.H.2, Mikhailidis D.P.1, Thompson C.S.1
University “Federico II”, Interdepartemental Centre for Preclinical and Clinical Research in Sexual Medicine (CIRMS), Naples, Italy
1 Royal Free Hospital NHS Trust, Dept. of Clinical Biochemistry, London, United Kingdom, 2&KDVH)DUP+RVSLWDO'HSWRI8URORJ\(QᚏHOG8QLWHG.LQJGRP
Introduction & Objectives: +\GURJHQVXOᚏGH+6 LVDQDWXUDOO\RFFXUULQJ JDVV\QWKHVL]HGIURP/F\VWHLQHE\WZRHQ]\PHVF\VWDWKLRQLQHದ˟V\QWKDVH &%6 DQGF\VWDWKLRQLQHˠO\DVH&6( 5HFHQWO\+6KDVEHHQSURSRVHG as a novel gaseous transmitter involved in several physiological and/or pathological processes. Our purpose was to investigate, in a vitro study on human corpus cavernosum tissue, the involvement of H2S in penile erection.
Introduction & Objectives: Penile erection results from the balance between relaxation and contractile mechanisms of the corpus cavernosum. The importance of nitric oxide (NO) in corpus cavernosal smooth muscle (CSM) relaxation and its reduction in erectile dysfunction is well documented. In contrast, the endogenous vasoactive peptide angiotensin II (Ang II), which is HOHYDWHGLQEORRGVDPSOHVWDNHQIURPᚐDFFLGKXPDQSHQLVKDVEHHQVXJJHVWHG WRLQGXFHUDEELW&60FRQWUDFWLRQ,QWKHSUHVHQWVWXG\ZHKDYHVWXGLHGWKHHᚎHFW of inhibiting Ang II receptor subtypes (AT1 and AT2) on Ang II-mediated rabbit CSM contraction. We have also determined the possible interaction between Ang II and NO in the modulation of cavernosal function.
Material & Methods: Human corpus cavernosum strips (HCC) obtained from male-to-female transsexual undergoing gender reassignment surgery were pre-contracted with phenylephrine (PE, 1µM) in organ baths. The ability of sodium hydrogen sulphide (NaHS, 1µM-10mM (stable donor of H2S) in relaxing these strips with (endothelium dependent) or without endothelium (endothelium independent) was evaluated. In addition, using GLᚎHUHQWFRQWUDFWLQJDJHQWVZHHYDOXDWHGLIWKHUHOD[LQJPHFKDQLVPVLQYROYH potassium channels and the Rho/RhoA kinase pathways. Results: Sodium hydrogen sulphide (NaHS, 1µM-10mM) relaxes HCC strips pre-contracted with phenylephrine in an endothelium dependent manner. )XUWKHUPRUHWKHUHOD[LQJHᚎHFWLVPRGLᚏHGE\FRQWUDFWLQJDJHQWVWKDWDFW through the modulation of potassium channels and/or the Rho/RhoA kinase pathways, thus demonstrating their involvement in the relaxing mechanism of NaHS. Conclusions: )RUWKHᚏUVWWLPHZHVKRZHGWKDW+6LVLPSOLFDWHGLQSHQLOH erection and might represent a novel therapeutic target for the treatment of erectile dysfunction.
Eur Urol Suppl 2008;7(3):216
Material & Methods: Experiments were performed with Ang II (10-8 – 10-5M, n=5) in the absence and presence of losartan (10-50$7UHFHSWRUDQWDJRQLVW 3'-50$7UHFHSWRUDQWDJRQLVW DQG/1$0(0-5012V\QWKDVH inhibitor) using normal rabbit CSM strips. Paired T-test were used for statistical analysis. Results: The results were expressed as a percentage of the phenylephrine 10-4M response and showed that Ang II caused a dose dependent contraction of CSM strips. This contractile response was inhibited by losartan (e.g. Ang ,,-6M & 10-70ZHUHUHGXFHGE\ SUHVSHFWLYHO\ EXWQRW 3',QFRQWUDVW/1$0(FDXVHGDDQGLQFUHDVHLQWKH$QJ II-induced contraction at 10-6M & 10-70SUHVSHFWLYHO\ Conclusions: Ang II mediated the contraction of rabbit CSM tissue via activation of AT1and not AT2 receptors. Furthermore, inhibition of the NO pathway with L-NAME potentiated Ang II-induced contractions. The enhanced $QJ,,UHVSRQVHFRXOGKDYHDGHOHWHULRXVHᚎHFWRQSHQLOHHUHFWLRQDQGPD\EH involved in erectile dysfunction.