Effects of steroids on oxytocin secretion by the human prostate in vitro.
Oxytocin (OT) concentrations are elevated in prostate tissue of patients with benign prostatic hyperplasia (BPH). Oxytocin specifically increases growth, 5 alpha-reductase activity and contractility in the prostate. In the rat prostatic OT concentrations are regulated by gonadal steroids, with androgens reducing but oestrogens increasing OT concentrations. The regulation of prostatic oxytocin in man is not understood. This study investigates the effects of gonadal steroids on oxytocin production by the human prostate. Primary explants (approx. 1 mm3) of prostate tissue from patients with BPH were incubated in Dulbecco's modified Eagle's media in the absence or presence of 10 nmol/L testosterone (T), 10 nmol/L dihydrotestosterone (DHT), T or DHT plus 100 nmol/L of the anti-androgen cyproterone acetate (CPA), 55 pmol/L diethylstilbestrol (DES), or DES plus DHT. The amount of oxytocin secreted into the media after 3 days was measured by radioimmunoassay. Testosterone and DHT significantly increased oxytocin concentrations secreted into the media from 0.86 +/- 0.11 ng/g of tissue (control) to 1.51 +/- 0.14 ng/g (p < 0.01) and 1.54 +/- 0.13 ng/g (p < 0.05), respectively. Incubation of tissue samples with CPA resulted in oxytocin concentrations similar to control levels. Treatment with DES caused a significant increase from 1.99 +/- 0.71 to 3.98 +/- 1.36 ng/g (p < 0.05). A similar increase was measured in media of tissue incubated in DES plus DHT (p < 0.001). The results demonstrate that, unlike the rat where androgens decrease oxytocin, in hyperplastic human prostate tissue both androgens and oestrogens increase oxytocin. This imbalance in the regulation of oxytocin may result in promoting prostatic overgrowth in the pathogenesis of BPH.
Assinder
S J
SJ
Department of Anatomy and Structural Biology, Andrology Research Group of Otago, School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand. stephen.assinder@stonebow.otago.ac.nz
Nicholson
H D
HD
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism / Q000502:physiology; D000818:Animals; D017373:Cyproterone Acetate / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010121:Oxytocin / Q000096:biosynthesis* / Q000378:metabolism; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors
D000726:Androgen Antagonists; D000728:Androgens; D013196:Dihydrotestosterone; D013739:Testosterone; D017373:Cyproterone Acetate; D010121:Oxytocin; D004054:Diethylstilbestrol