Oxytocin and the human prostate in health and disease.

Oxytocin is a peptide hormone produced by the neurohypophysis. The discovery that the peptide is produced locally within the male and female reproductive tracts has raised the possibility that oxytocin may have paracrine and autocrine actions outside of the nervous system. Oxytocin and its receptor have been identified in the human prostate. The prostate is an androgen-dependent organ whose function is to secrete components of the seminal fluid. Oxytocin has been shown to modulate contractility of prostate tissue and also to regulate local concentrations of the biologically active androgens. Oxytocin has also been shown to regulate cell growth. Prostate disease is common and results from abnormal growth of the gland. Oxytocin concentrations are altered in both benign and malignant prostate diseases and in vitro studies suggest that the peptide may be involved in the pathophysiology of these diseases.

The trends in prostate specific antigen usage amongst United Kingdom urologists--a questionnaire based study.

BACKGROUND: Worldwide, the use of prostate specific antigen (PSA) testing as a screen for prostate cancer is contentious. Whilst there is no National UK Screening programme, many men undergo opportunistic screening. This study investigates UK urologist's usage of PSA and the awareness surrounding the Department of Health (DoH) PSA guidelines. METHODS: Urologists were sent a questionnaire regarding PSA cut-off values. RESULTS: Of the 733 urologists eligible to participate in this study 346 returned completed questionnaires giving a response rate of 47%. The most commonly generally used age-related PSA cut-off values (36% of respondents) are--3.5 ng/ml for 50 - 59 year olds, 4.5 ng/ml for 60 - 69 year olds and 6.5 ng/ml for over 70 year olds. Two-thirds (58%, 200/346) of respondents were aware of the DoH PSA guidelines but only 20% (n = 69/346) follow these guidelines. The majority of respondents (68%, n = 234/346) used higher PSA cut-offs than recommended by the DoH. The level of compliance showed marked regional variation with a range from 7% to 44% (median 19%). In addition, it was apparent that lower PSA cut-off values were used in private practice as opposed to the National Health Service. CONCLUSION: A nationwide lack of agreement on PSA cut-off values may generate a variable standard of care both regionally and in NHS versus private practice. Generally, higher PSA cut-off values are being used than recommended by the DoH guidance.

Quantitative analysis of epithelial cells in urine from men with and without urethritis: implications for studying epithelial: pathogen interactions in vivo.

BACKGROUND: Epithelial cells in first catch urine (FCU) specimens from 87 men with and without urethritis were quantified. Epithelial cells were broadly categorised into transitional and squamous populations using morphological characteristics and immunostaining with anti-pan leukocyte and anti-cytokeratin monoclonal antibodies. FINDINGS: The majority (77/87 = 89%) of samples contained both transitional (76/87 = 87%; range 1 x 10(4) - 6 x 10(5), median 6 x 10(4)) and squamous (57/87 = 66%; range 1 x 10(4) - 8 x 10(5), median 2 x 10(4)) epithelial cells. The number of transitional cells correlated with the number of squamous cells (Spearman's rho = 0.697 p < 0.001). Squamous, but not transitional, cell numbers correlated with leukocyte numbers (Spearman's rho = 0.216 p = 0.045 and rho = 0.171 and p = 0.113, respectively). However there was no significant difference in epithelial cell numbers between men with and without urethritis. Nevertheless, some men with urethritis had relatively high numbers of transitional cells in their FCU. Transitional cells were morphologically heterogeneous and appeared to display complex cytokeratin phenotypes. CONCLUSION: Further studies are required to explore the complexity of epithelial cell populations in urine. These would provide novel opportunities for studying cellular interactions of C. trachomatis in male urethral infections, about which little is currently known.

The effect of oxytocin on cell proliferation in the human prostate is modulated by gonadal steroids: implications for benign prostatic hyperplasia and carcinoma of the prostate.

BACKGROUND: Oxytocin (OT) is implicated in regulating prostate growth. OT concentrations are increased in benign, and decreased in malignant prostate disease. This study investigated whether the altered concentrations of OT present in prostate disease affect the proliferation of malignant and non-malignant human prostate cells. METHODS: The effects of varying concentrations of OT and gonadal steroids on cell proliferation of non-malignant prostatic epithelial (PrEC) and stromal (PrSC) cells and androgen dependent (LNCaP) and independent (PC-3) malignant cell lines were assessed. RESULTS: OT (>0.5 nmol . L(-1)) had no effect on PrEC proliferation when cells were cultured alone. When co-cultured with PrSC and gonadal steroids, OT inhibited epithelial cell proliferation. OT inhibited PrSC proliferation, when cells were cultured alone. When PrSC were co-cultured in the presence of estrogen physiological concentrations of OT were inhibitory. No effect on cell proliferation was observed with higher concentrations of OT. OT did not affect the proliferation of malignant cell lines in the absence of androgens but, in the presence of testosterone, low concentrations of OT (<1 nmol . L(-1)) stimulated proliferation of PC-3 cells. Disruption of caveolae in the plasma membrane removed the inhibitory effect of OT on PrSC proliferation but did not affect the stimulatory effect of OT on PC-3 cells cultured in the presence of androgens. CONCLUSIONS: Changes in prostatic concentrations of OT that occur with aging and malignant disease may act to facilitate cell proliferation. The localization of the OT receptor within the plasma membrane modulates OT's proliferative response in the prostate.

Oxytocin--its role in male reproduction and new potential therapeutic uses.

Oxytocin (OT) is traditionally thought of as a "female" neurohypophysis hormone due to its role in parturition and milk ejection. However, OT is recognized as having endocrine and paracrine roles in male reproduction. At ejaculation, a burst of OT is released from the neurohypophysis into the systemic circulation and stimulates contractions of the reproductive tract aiding sperm release. There is conclusive evidence that OT is synthesized within the mammalian testis, epididymis and prostate and the presence of OT receptors (OTRs) through the reproductive tract supports a local action for this peptide. OT has a paracrine role in stimulating contractility of the seminiferous tubules, epididymis and the prostate gland. Interestingly, OT has also been shown to modulate androgen levels in these tissues via stimulation of the conversion of testosterone to dihydrotestostone (DHT) by 5alpha-reductase. The elucidation of OT's role in male reproduction has suggested a number of potential therapeutic uses for this hormone. Exogenous administration of OT has, in some cases, been shown to increase the numbers of ejaculated sperm, possibly by stimulating contractions of the reproductive tract and thus aiding sperm passage. Within the prostate, OT has been shown to affect gland growth both directly and via its interaction with androgen metabolism. Prostate pathologies due to unregulated cell proliferation/growth, such as benign prostatic hyperplasia and cancer, are unfortunately very common and few effective treatments are available. Greater understanding of paracrine growth mediators, such as OT, is likely to provide new mechanisms for treating such pathologies.

Lack of compliance by UK andrology laboratories with World Health Organization recommendations for sperm morphology assessment.

BACKGROUND: Sperm morphology is known to correlate with the probability of conception both in vitro and in vivo, but the assessment of sperm morphology in the laboratory remains problematic. The 4th edition (1999) of the World Health Organization (WHO) Laboratory Manual has attempted to improve matters by giving rigorous recommendations regarding sperm morphology assessment. However, it is unknown how well these recommendations have been implemented in practice. METHODS: A survey of the methods used to undertake the assessment of sperm morphology during semen analysis was undertaken in 37 laboratories in the UK. RESULTS: In total, only two laboratories (5%) were compliant with all current WHO guidelines regarding morphology assessment, including methods of staining and observation, classifying and sampling methods, and the participation in internal and external quality control programmes. CONCLUSION: These results illustrate an urgent need for education and training initiatives to encourage laboratories to become compliant with current WHO guidelines for sperm morphology assessment.

Oxytocin, oxytocin-associated neurophysin and the oxytocin receptor in the human prostate.

Oxytocin has been implicated in the regulation of prostate growth. However, the cellular localisation of oxytocin in the normal and diseased human prostate is not known. Oxytocin, oxytocin-associated neurophysin and oxytocin receptor were detected by immunohistochemistry in tissues from patients undergoing routine prostatectomy and in normal human prostate epithelial and stromal cell lines. Western blot analysis detected a single band at 14 kDa with neurophysin antiserum and a 66-kDa band with oxytocin receptor antiserum in epithelial and stromal cell lines. Similar sized bands were also detected in extracts of hyperplastic and adenocarcinomic prostate tissues. Oxytocin, oxytocin-associated neurophysin and oxytocin receptor were present in stromal and epithelial cell lines and in tissue from patients with benign prostatic hyperplasia. The peptides were localised predominantly to the epithelial cells, although discrete areas of stromal staining were also observed. There was a significant difference in the intensity of oxytocin-staining between tissue displaying benign prostatic hyperplasia and invasive carcinoma, with less immunoreactivity being present in the malignant epithelial cells. Thus, oxytocin and its neurophysin and receptor are present in epithelial and stromal cells of the human prostate. Oxytocin expression is reduced with tumour progression and may provide a marker for invasive disease.

Can the Internet widen participation in reproductive medicine education for professionals?

BACKGROUND: Traditional campus-based models of education are unsuitable to many, particularly if in full-time employment supporting families, whereas the Internet now permits new models of education. Following an iterative process of development and evaluation in 2001, the University of Bristol launched a masters programme covering reproduction and development delivered principally over the Internet. METHODS: Students attend short biannual residential workshops and the rest of the course is delivered online. In 2003, the 20 active students were invited to complete a structured online questionnaire. RESULTS: The 18 students completing the questionnaire identified distance learning as the key factor in their course selection. Most students felt that residential workshops aided subsequent electronic communication. Discussion of ideas is an essential component of postgraduate courses and web-based discussion forums appeared to provide an acceptable medium for this. The use of web-based audio lectures and computer-assisted assessments was well received. Also these systems may reduce disadvantages overseas students encounter when completing assessments in their non-native language. CONCLUSIONS: The overall positive response from students (and their tutors) to using the Internet for multiprofessional reproductive medicine education is encouraging and has wider potential in the future.