Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. The X-ray crystal structure of a fully active, truncated form of human arginase II complexed with a boronic acid transition state analogue inhibitor has been determined at 2.7 A resolution. This structure is consistent with the hydrolysis of l-arginine through a metal-activated hydroxide mechanism. Given that human arginase II appears to play a role in regulating l-arginine bioavailability to NO synthase in human penile corpus cavernosum smooth muscle, the inhibition of human arginase II is a potential new strategy for the treatment of erectile dysfunction [Kim, N. N., Cox, J. D., Baggio, R. F., Emig, F. A., Mistry, S., Harper, S. L., Speicher, D. W., Morris, S. M., Ash, D. E., Traish, A. M., and Christianson, D. W. (2001) Biochemistry 40, 2678-2688]. Since NO synthase is found in human clitoral corpus cavernosum and vagina, we hypothesized that human arginase II is similarly present in these tissues and functions to regulate l-arginine bioavailability to NO synthase. Accordingly, hemodynamic studies conducted with a boronic acid arginase inhibitor in vivo are summarized, suggesting that the extrahepatic arginase plays a role in both male and female sexual arousal. Therefore, arginase II is a potential target for the treatment of male and female sexual arousal disorders.
The goal of this study was to investigate the effects of medical castration (luteinizing hormone-receptor hormone [LH-RH] agonist treatment) or surgical castration on erectile function in an animal model. New Zealand White male rabbits were either kept intact (control); surgically orchiectomized; or treated for 2, 4, or 8 weeks with the LH-RH agonist leuprolide acetate (107 microg/kg/mo). At 2 weeks, plasma testosterone levels of orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of intact control animals, respectively. Erectile function was assessed by continuously recording systemic arterial pressure (SAP) and intracavernosal blood pressure (ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at varying frequencies (2.5-32 Hz). Androgen deprivation by surgical (orchiectomy) or medical (leuprolide acetate) castration reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil (10 microg/kg) did not enhance ICP in surgically orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by surgical or medical castration. Further, Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. These data demonstrate that androgen deprivation achieved by surgical or medical castration adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction.
Introduction In Korea, although male sexual problems have been relatively well addressed, few surveys have been conducted on female sexual dysfunction (FSD) in the general population. In the present study, we investigated the prevalence and identified the risk factors of sexual dysfunction in young Korean women. Aim To evaluate the prevalence and to identify the risk factors of FSD in young Korean women. Methods A total of 47,000 women were initially approached. All received an e-mail requesting that they participate in a Web-based survey. The participants were asked to complete a questionnaire requesting detailed medical and sexual histories, which included the questions contained in the Korean version of the Female Sexual Function Index questionnaire. Main Outcome Measures The prevalence of FSD in young Korean women in the different age groups and risk factors for developing FSD. Results A total of 504 women of average age 28.5 years (18–52 years) were evaluated during this survey. Setting the cutoff score for FSD using a receiver operating characteristic curve of our data as 25.0 points, 43.1% of women under 40 years old reported FSD. FSD was detected as a desire problem in 44.0% of women, an arousal problem in 49.0%, a lubrication problem in 37.0%, an orgasm problem in 32.0%, a satisfaction problem in 37.0%, and a pain problem in 34.6%. Risk factors for FSD as determined by logistic regression analysis were increasing age, a low frequency of sex, depression, a sexually abused history, and voiding dysfunction. Conclusions The prevalence of FSD in Korean young women was common and comparable to those reported worldwide.
Estradiol is crucial for maintaining optimal vaginal blood flow in the rat. Lower levels of plasma estradiol trigger compensatory ERalpha up-regulation.
Male germ cell development includes mitotic and meiotic cell divisions that are followed by dramatic morphological changes resulting in the production of spermatozoa. Genetic evidence has indicated that the DAZ family genes are critical for successful male germ cell development in diverse animals as well as humans. In the present study, we investigated the cellular functions of Dazl in the mouse male germ cells. We identified a specific interaction of Dazl with the dynein light chain, a component of the dynein-dynactin motor complex. The subcellular distribution of Dazl was microtubule-dependent and a selected number of Dazl-bound mRNAs could accumulate in the perinuclear area. Based on these results, we propose that Dazl may play a role in transport of specific mRNAs via dynein motor complex. The Dazl-bound mRNAs may be stored at specific sites and would be available for future developmental processes. Our study revealed the presence of an active mRNA transport system in mouse male germ cells.
Premature ejaculation (PE) is suspected to be the most prevalent male sexual complaint, and the prevalence of PE is considerably high also in the younger generation. We investigated the PE prevalence based on the Diagnostic and Statistical Manual of Mental Disorders (4th ed text revision; DSM-IV-TR) definition and the risk factors of PE in Korean young men via Internet survey. Subjects (n 5 3980) aged from 20 to 59, who performed sexual intercourse more than once a month during the past 6 months were asked to participate in this study. Participants were asked to complete a questionnaire that consisted of questions on general, medical, and sexual history related to ejaculation. A total of 600 subjects were included in this study. PE prevalence was found to be 18.3%. Prevalences were not significantly different across age groups, after excluding subjects with erectile dysfunction (ED). Educational level, marital status and duration, average income, sexual orientation, smoking, alcohol consumption, and circumcision status showed no difference in the PE and non-PE groups. Partners perceived satisfaction rates were 45.0% in the PE group and 63.9% in the non-PE group. Significant differences were found between the PE and non-PE groups in terms of ED, obesity, and depression prevalence. However, multiple logistic regression analysis revealed that the significant risk factors of PE were age and the frequency of conversations with partners about sexual intercourse. This Internet-based study is limited because participants probably represent a selected population of Internet users with non-representative educational and socioeconomic profiles. This study is the first to report the prevalence of both self-reported PE and PE on the basis of the DSM-IV-TR definition in the Korean population. This study demonstrates that PE in Korea is as prevalent as it is in European countries and the United States.
Our data suggest that early inhibition of Rho-kinase after cavernous nerve crush injury may prevent corporal apoptosis and fibrosis by suppressing the Akt/Bad/Bax/caspase-3 and LIMK2/cofilin pathways, preventing corporal veno-occlusive dysfunction and erectile dysfunction.
The study demonstrates that urodynamic studies are well tolerated by male and female patients in all age groups. However, emotional support depending on gender prior to the urodynamic procedure might enhance the level of patient cooperation.
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