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1、The Prostate and Benign Prostatic HyperplasiaAccessory Sex Glands Prostate Seminal vesicles Cowpers glandsWe Will Consider The structure of the prostate and its role in continence The mechanism of ejaculation and the role of the prostatic innervation The role of the secretory products of the prostat
2、e in the prostatic fluidThe Structure of the ProstateMcNeals Hypothesis Transitional zone the site of origin of BPH Central zone Wolffian duct origin cf vasa and seminal vesicles Peripheral zone the site of origin of 75% of cancers Anterior fibromuscular stromaOrigin Peripheral and central zones - U
3、G sinusDHT Central zone Wolffian ductsTestosteroneOrigin of Circulating TestosteroneTestosterone UptakeDevelopment of the Prostate DHT formed mainly in epithelial cells DHT diffuses to stroma (most of the androgen receptors) Stromal nuclei produce growth factors Growth factors drive epithelial cells
4、Stromal epithelial interactionSummaryGrowth FactorsNormallybFGF EGF TGF 20%TGF inhibitory80%stimulatoryThe Pre-prostatic SphincterProstatic InnervationClassical adrenergic cholinergicNANC 5-HT Dopamine- hydroxylase VIP NPY Leu-encephalin Met-encephalin CGRP Sustance PAlpha Adrenergic Innervation-adr
5、energic receptors 98% in stroma alpha-1 90% alpha-2 10%alpha 1a 60%Innervation Cholinergic - epithelial secretion Adrenergic - smooth muscle contraction Neuroendocrine cells - serotonincalcitoninTSHsomatostatin- regulation of secretion, cell growth NANC - ?Bladder Neck v Preprostatic SphincterBladde
6、r NeckBoth sexes At bladder neck Cholinergic innervation Continence mechanismPreprostatic sphincterMales Supraverumontanal Adrenergic innervation Genital sphincterEjaculation - Mechanism Spermatozoa and prostatic fluid, then seminal vesicle fluid = Emission Antegrade despite competent urethral mecha
7、nism Voiding difficult with an erection and immediately after ejaculationBladder Neck Tightens U/SUrethral Pressure ProfileEjaculation Sequence Bladder neck tightens Emission of vasal ampullary sperm Contraction of bulbospongiosus Contraction of prostatic smooth muscle Urethral sphincter mechanism o
8、vercome Further contraction of prostate and seminal vesicle contractionSeminal Plasma2ml seminal vesicle secretion 0.5ml prostatic secretion 0.1ml Cowper,s glands and glands of LittrRole of Seminal PlasmaOptimise fertilisation (ejaculated sperm v aspirated sperm) protective effect enhance motility a
9、nd survival directly Protective effect on urinary tract biological esp. Zn, spermine, Ig mechanical washing LubricationProstatic SecretionProteinsAcid phosphatase PSA Leucine aminopeptidase Diamine oxidase Glucuronidase Plasminogen activator Complement C3 and C4 Transferrin, transferritin Growth fac
10、tors Annexin 1Non proteinsCitrate Spermine Spermidine Putrescine Zinc Myoinositol CholesterolFunctions Zinc - 4 structure of sperm chromatin PSA semen liquefaction Otherwise?Non-ProteinsCitrate 240-1300 times concentration elsewhere Zinc PolyaminesExist as a complex to maintain electrochemical neutr
11、alityalso in uniquely high concentrationsBenign Prostatic HyperplasiaBPH - MisconceptionsGeneralised disease of the prostate due to hormonal derangement which leads to enlargement of the gland which causes compression of the urethra leading to symptomsAetiology Age Functioning testes Prostate normal
12、 to begin withPossibly a series of genetic hits which, with further hits, will lead to cancerOther Factors Racial - american blacks v orientals Dietary - yellow vegetables, western dietPathogenesisAndrogens - permissiveStromal epithelial interaction normal 2:1, BPH 3 or 4:1 major change is connectiv
13、e tissueStromal-Epithelial Ratio in BPHEpithelium 25%+/-Stroma 75%+/- connective tissue 50%+/- smooth muscle 25%+/-Pathogenesis - 2Micronodules:transition zone laterally micronodules in periurethral zone posteriorlyPathogenesis - 3Transition zone enlarges laterally on each side stroma and epithelium
14、Periurethral zone enlarges posteriorly stroma only firoblasts transforming to smooth muscle cells embryonic reawakeningHistologyPosteriorLateralAndrogens and BPH Permissive in vivo and in vitro Growth factors are just as importantGrowth Factors and the ProstateNormalbFGFEGF stimulatoryTGFTGF - inhib
15、itoryGrowth Factors and the ProstateBPHbFGF stromal autocrine stimulatoryKGF stromal paracrine stimulatoryTGF1 stromal autocrine/paracrine inhibitoryTGF2 epithelial autocrine/paracrine inhibitoryIGF stromal paracrine stimulatoryGrowth Factors and the Prostate?TGF upregulated by declining serum testosterone which then secondarily affects other growth factors?lifelong ejaculation/voiding affecting the bendAgeingBPH Detrusor instability Impaired detrusor contra
