The induction of new ductal growth in adult prostatic epithelium in response to an embryonic prostatic inductor

Tissue recombinants were prepared with a single epithelial ductal tip from adult prostate and mesenchyme from either the embryonic urogenital sinus or adult urinary bladder. Recombinants were grown in vivo beneath the renal capsule of male hosts. After 4 weeks of in vivo growth, extensive growth of arborizing ducts was apparent in recombinants composed of urogenital sinus mesenchyme and a single adult prostatic ductal tip. One-dimensional polyacrylamide gel electrophoresis indicated that these recombinants contained many of the proteins of the mature prostate. Heterospecific recombinants (rat urogenital sinus mesenchyme and mouse prostatic epithelium) showed the ductal tissue to be derived solely from the prostatic epithelium. In recombinants of a prostatic ductal tip with mesenchyme from the urinary bladder, ductal growth was absent, the ductal tip was maintained as a single, discrete, epithelial structure, and the protein composition of these recombinants more closely resembled that of the bladder. The results demonstrate that the epithelial cells of the adult prostate can participate in new ductal growth in response to an embryonic prostatic inductor. These data provide experimental evidence to support the hypothesis that human benign prostatic hyperplasia may result from the anomalous reactivation of embryonic growth potential in the adult prostate.     

Semiquantitative morphology of human prostatic development and regional distribution of prostatic neuroendocrine cells

BACKGROUND: The neuroendocrine cells of the human prostate have been related to proliferative disorders such as prostatic cancer. Their origin, distribution, and development have therefore been studied and discussed in terms of current stem cell concepts in the prostate. METHODS: Prostatic tissue specimens (n = 20) from human fetuses (n = 8), prepubertal and pubertal children (n = 8) and mature men (n = 4) were studied immunohistochemically using antibodies directed against neuroendocrine, epithelial as well as secretory markers. Semiquantitative computer-assisted evaluation of different epithelial and stromal components based on stereological principles was performed on azan-stained sections representative of all developmental stages. RESULTS: By the end of gestational Week 9, neuroendocrine (NE) cells appear in the epithelium of the urogenital sinus and are subsequently closely associated with the formation of urethral prostatic buds. The fetal and postnatal distribution pattern of NE cells within the gland is characterized by a relatively constant number of cells per gland similar to prostatic smooth muscle cells. Likewise, a density gradient exists with the highest density in the large collicular ducts and almost no NE cells in subcapsular peripheral acini. In peripheral ducts, the distribution is random. Maturation of the NE cells precedes that of the secretory cells by about 10-16 years. CONCLUSIONS: A second prostatic stem cell lineage, different from the urogenital sinus (UGS)-lineage is hypothesized originating from immature neuroendocrine cells. Being morphologically indistinguishable from the UGS-derived prostatic secretory cell lineage, it gives rise to neuroendocrine cells. Their presence is apparently important for proliferation regulation of the UGS-derived lineage of the prostate.     

Morphologic and biochemical alterations in rat prostatic tumors induced by fetal urogenital sinus mesenchyme

Because fetal urogenital sinus mesenchyme (UGM) has been found to be highly inductive when recombined with normal adult prostate tissues or normal and neoplastic bladder epithelium, we investigated whether fetal UGM also interacts with established hormone-responsive and unresponsive rat Dunning and Nb prostate tumors. Our results indicate that: 1) fetal UGM acts directly on selected rat prostatic tumors by inducing histomorphologic changes (e.g., inducing acinar ductal structures and secretory activity) in the tumors toward more differentiated forms resembling that of the adult prostate gland; 2) fetal UGM either increased the growth rate of or maintained the sizes of three of the four interacting rat prostatic tumors; and 3) fetal UGM markedly reduced the lactate dehydrogenase activity of Nb-autonomous tumor toward a level comparable to that of the normal rat prostate gland. Our data suggest that fetal UGM can directly affect the growth and differentiative functions of selected rat prostatic tumors.     

Stromal-epithelial interactions: II. Regulation of prostatic growth by embryonic urogenital sinus mesenchyme

Embryonic urogenital sinus mesenchyme (UGM) has been demonstrated previously to be a potent inductor of prostatic morphogenesis and functional differentiation when associated with either embryonic urogenital sinus epithelium (UGE) or urothelium derived from adult urinary bladder (ABLE) and grown in male hosts. To determine the role of mesenchyme in prostatic acinar growth, homotypic tissue recombinants of 16-day-old embryonic mouse urogenital sinus mesenchyme and epithelium (UGM_mouse + UGE_mouse) were prepared in which the relative amounts of UGM to UGE were varied from approximately 0.1:1 to 100: 1. Recombinants were grown for 1 month in intact male hosts after which the amount of acinar growth was assessed by histological analysis and by determination of wet weight and DNA content. The latter criteria are valid measures of acinar content of histologically normal prostatic tissue because the rodent prostate is composed of greater than 80% ductalacinar tissue. From this analysis the amount of acinar growth was found to be determined by the amount of mesenchymal tissue and was independent of the amount of epithelium utilized to prepare the tissue recombinants. Similarly, the magnitude of growth in heterospecific rat-mouse tissue recombinants prepared with urogenital sinus epithelium or adult bladder epithelium (ABLE) and urogenital sinus mesenchyme (UGM_mouse + UGE_rat, UGM_mouse + ABLE_rat UGM_rat + UGE_mouse, or UGM_rat + ABLE_mouse) is determined by the source of UGM. Although the initial DNA content per UGM is comparable between mouse and rat, the overall acinar growth induced by UGM_rat is about 10-fold greater than that induced by UGM_mouse when recombined reciprocally with UGE_mouse and UGE_rat, respectively. These results suggest that UGM is of fundamental importance as a regulator of prostatic epithelial growth. The relevance of this finding to the development of human benign prostatic hyperplasia is discussed.     

Antagonistic effects of cyproterone acetate and oestradiol on the development of the fetal rat prostate gland induced by androgens in organ culture

The influence of cyproterone acetate and 17beta-estradiol on the induction of the rat prostate gland by androgens has been investigated in organ culture. The gland develops from its "anlage," the urogenital sinus, as epithelial buds projecting from the urogenital epithelium into the surrounding mesenchyme. In 16.5-day-old male sinuses explanted in organ culture, testosterone or dihydrotestosterone induced such buds de novo; cyproterone acetate or 17beta-estradiol combined with the androgens competitively inhibit the bud formation in most explants. In contrast, in 18.5-day male sinuses both anti-androgens are ineffective, and prostatic buds develop. The difference in response suggests that in the older tissue, exposure to endogenous testosterone before explantation has already set in motion events leading to the differentiation of the gland that are irreversible.     

Evidence of stem cells in the adult prostatic epithelium based upon responsiveness to mesenchymal inductors

Ductal tips approximately 300 μm in length from adult rat dorsal (DP), lateral type 1 (L1), and lateral type 2 (L2) prostates were combined with mesenchyme from the embryonic urogenital sinus (UGM), neonatal seminal vesicle (SVM), or neonatal bulbourethral gland (BUGM) and grafted underneath the renal capsule of syngeneic male hosts. Following 1 month of in vivo growth, all tissue recombinants formed large masses of prostatic ductal tissue, which represented massive growth of the original population of prostatic epithelial cells. Examination of secretory protein expression in these tissue recombinants indicated that each mesenchyme influenced secretory function in the adult prostatic epithelium in a characteristic way. SVM maintained expression of DP-1 and probasin in prostatic ducts of DP, L1, and L2, which normally express these proteins. BUGM induced expression of C3 in prostatic ducts of the DP, L1, and L2, which normally do not express C3. UGM induced the expression of DP-1, probasin, and C3 in prostatic ducts from all dorsal-lateral lobes. Mesenchymal induction of massive epithelial growth, new ductal branching morphogenesis, and change in prostatic lobe identity are indicative of the presence of stem cells in adult prostatic epithelium because high proliferative capacity, tissue regeneration, and pluripotency (change in functional differentiation) are hallmarks of stem cells. © 1996 Wiley-Liss, Inc.     

Unopposed c-MYC expression in benign prostatic epithelium causes a cancer phenotype

BACKGROUND: We have sought to develop a new in vivo model of prostate carcinogenesis using human prostatic epithelial cell cultures. Human prostate cancers frequently display DNA amplification in the 8q24 amplicon, which leads to an increase in the copy number of the c-MYC gene, a finding that suggests a role for c-MYC in human prostate carcinogenesis. In addition overexpression of c-MYC in transgenic mouse models results in prostatic carcinogenesis. METHODS: We took advantage of the ability of retroviruses to integrate foreign DNA into human prostatic epithelium (huPrE) to generate cell lines that overexpress the c-MYC protooncogene. These cells were recombined with inductive rat urogenital sinus mesenchyme and grafted beneath the renal capsule of immunocompromised rodent hosts. RESULTS: The resultant tissue displayed a phenotype consistent with a poorly differentiated human prostatic adenocarcinoma. The tumors were rapidly growing with a high proliferative index. The neoplastic cells in the tumor expressed both androgen receptors (AR) and prostate-specific antigen (PSA), both characteristic markers of human prostate cancers. Microarray analysis of human prostatic epithelial cells overexpression c-MYC identified a large number of differentially expressed genes some of which have been suggested to characterize a subset of human cancers that have myc overexpression. Specific examples were confirmed by Western blot analysis and include upregulation of c-Myb and decreased expression of PTEN. Control grafts using either uninfected huPrE or using huPrE cells infected using an empty vector expressing a green fluorescent protein tag gave rise to well differentiated benign prostatic glandular ducts. CONCLUSIONS: By using a retroviral infection strategy followed by tissue recombination we have created a model of human prostate cancer that demonstrates that the c-MYC gene is sufficient to induce carcinogenesis.     

Prostatic development, cytodifferentiation and growth: epithelial-mesenchymal interaction and heterogeneity of prostatic cellular activity

Prostatic growth and hormonal effects on the prostate play a basic role in the pathogenesis of abnormal proliferative diseases (i.e. benign prostatic hyperplasia and prostatic carcinoma). During the embryonic period, the prostate is organized through the budding and branching of the epithelial cords into the urogenital sinus mesenchyme. The urogenital sinus mesenchyme has an inductive potential for the prostatic epithelial development and cytodifferentiation under the influence of androgen and an epithelial-mesenchymal interaction. In this interaction, mesenchymal cells are considered as a mediator of hormonal action on epithelial cells. Postnatal prostatic growth is obtained further ductal branching morphogenesis and regulated by the epithelial-mesenchymal interaction, androgen, and epithelial/mesenchymal ratio. Castration-induced degeneration, and androgen-induced regeneration of the glandular architecture of the mouse prostate were investigated by microdissection techniques that permitted precise quantitation of the numbers of the terminal ductal tips and ductal branch-points. During the first 15 days after birth, active branching morphogenesis occurred as a result of focally high levels of DNA synthesis confined almost exclusively to the distal tips of the branching ducts. Following castration about 35% of the ductal tips and branch-points were lost in distal regions (usually near the capsule). By contrast, in more proximal regions of the prostate the ducts survived in an atrophic condition. The lost distal ductal morphology completely regenerated following administration of testosterone propionate (TP) to the castrated males. Whole-mount autoradiography demonstrated that labelling intensity reached a maximum on the third day of TP treatment in distal ductal areas. Recognition of the mesenchymal-epithelial interaction and heterogeneities in the morphogenesis, androgen dependency, and DNA synthetic activity within the prostatic architecture is fundamental to understanding the mechanism of androgenic regulation of normal or abnormal prostatic growth and development.     

Increased expression of tumor-associated trypsin inhibitor, TATI, in prostate cancer and in androgen-independent 22Rv1 cells

OBJECTIVES: Tumor-associated-trypsin inhibitor (TATI) is frequently coexpressed with trypsinogen in tumors. Recently, we found expression of trypsinogens in prostate cancer. We have now studied whether TATI is also expressed in prostate cancer and if TATI expression is associated with Gleason grade, proliferation, and neuroendocrine differentiation. METHODS: Expression of TATI and prostate-specific antigen (PSA) was studied by immunohistochemistry and in situ hybridization, and that of chromogranin A (CgA) and Ki-67 by immunohistochemistry. Immunofluorometric assays were used to quantify TATI and PSA in serum from prostate cancer patients and in medium of 22Rv1 prostate cancer cells. RESULTS: TATI expression was weak in benign prostatic epithelium and moderate to strong in prostate cancer and high-grade prostatic intraepithelial neoplasia. There was no correlation between TATI and Ki-67 immunostaining in a tissue microarray of 115 prostate cancer cores, but strong expression of TATI was associated with higher Gleason grade (p=0.002) and CgA immunostaining intensity (p=0.012). Serum TATI was elevated in 44% (29 of 66) of patients with prostate cancer, and the levels correlated with serum PSA (p<0.0001, r=0.306). DU145, PC-3, LNCaP, and 22Rv1 cells contained TATI mRNA as determined by RT-PCR, but only 22Rv1 cells produced detectable TATI protein. The synthetic androgen R1881 decreased secretion of TATI from 22Rv1 cells. CONCLUSIONS: We demonstrate for the first time that TATI is expressed in the benign and malignant prostate. Increased TATI protein expression is found in high-grade tumors and in 22Rv1 cells in which it is regulated by androgens.     

The Androgen Cascade in Ageing Men: Blessing or Curse?

Dihydrotestosterone (DHT) is a dominant force in the development of the adult prostate. The action of DHT is critical in modulating the interaction of epithelial cells in the urogenital sinus mesenchyme during the organogenesis of the prostate. During adolescence, DHT is required to complete the normal growth phase of the prostate. In older men, if the response to DHT is altered, the resulting population of cells may be dominated by the transient proliferation of intermediate cells that are very sensitive to DHT for their ‘amplifying’ potential. In benign prostatic hyperplasia, these mechanisms are disturbed and the usual control of final stromal and epithelial cell mass is ineffective. The importance of the two isozymes of 5α reductase in regulating the continuing stromal:epithelial cell balance might provide a good scientific basis for moderating both pathways in an attempt to alter the clinical consequences of abnormal prostate growth.     

Androgenic induction of DNA synthesis in prostatic glands induced in the urothelium of testicular feminized (Tfm/Y) mice

It has been shown previously that wild-type urogenital sinus mesenchyme can induce the formation of prostate-like glandular structures in urinary bladder epithelium derived from adult Tfm (testicular feminization) mice. Total DNA synthesis within these tissue recombinants has been shown biochemically to be androgen sensitive. To determine which tissue (epithelium or stroma) accounts for this androgen-dependent DNA synthesis, an autoradiographic study was performed with tissue recombinants composed of rat wild-type urogenital sinus mesenchyme (UGM) associated with bladder epithelium from either wild-type (BLE) or Tfm mice (Tfm BLE). Both types of recombinants were grown under the kidney capsule of male athymic nude mice for 4 weeks. The hosts were then castrated, and 2 weeks later were treated with either testosterone propionate (TP), TP plus cyproterone acetate (CA), or oil vehicle for 3 days. DNA synthetic activity was measured through analysis of labelling index (LI) after incorporation of 3[H]-thymidine in vivo. For both UGM + BLE and UGM + Tfm BLE recombinants thymidine incorporation in epithelial cells greatly exceeded that of the stromal cells. TP stimulated epithelial LI to a similar degree (about 50- to 200-fold greater than controls) in both UGM + BLE and UGM + Tfm BLE recombinants; CA antagonized the effect of TP. Nuclear 3H-DHT binding was observed autoradiographically within the epithelial cells of the induced epithelium of UGM + wild-type BLE recombinants, but not within epithelium of UGM + Tfm BLE recombinants. Wild-type mesenchymal cells in both tissue recombinants showed specific nuclear 3H-DHT uptake. Thus, the proliferative effect of androgens upon prostatic epithelium is not a direct effect mediated by intra-epithelial androgen receptors, but rather it appears to be elicited indirectly via regulatory influences from androgen-receptor-positive stromal cells.     

Interferon-gamma induces neuroendocrine-like differentiation of human prostate basal-epithelial cells

BACKGROUND: Prostatic neuroendocrine (NE) cells are intraglandular hybrid epithelial-neural-endocrine cells that express and secrete numerous hormones and neuropeptides, which presumably regulate growth, differentiation, and secretory activity of the prostatic epithelium. This specialized cell type appears to differentiate from a common basal/precursor/stem cell that also gives rise to the secretory epithelium. In order to elucidate mechanisms of NE-differentiation the effects of type 1 (alpha, beta) and type 2 (gamma) interferons (IFNs) on human prostate basal cells (PrECs) were evaluated. METHODS AND RESULTS: Application of alpha/beta IFN increased the expression of the cell-cycle inhibitor p21(CIP1) and inhibited DNA synthesis, while only IFN-gamma led to increased apoptosis, cell-cycle inhibitor p27(KIP1) upregulation, and differentiation of PrECs into NE-like cells. In vitro differentiated NE-like cells expressed the glycolytic enzyme neuron-specific enolase (NSE) and chromogranin A (CgA), known markers of NE-cells in vivo in the prostate. These NE-like cells also changed cytokeratin (CK) expression patterns by upregulating CK 8/18, predominantly found in terminally-differentiated secretory luminal/NE epithelial cells. CONCLUSIONS: IFN-gamma produced locally in the prostate by basal cells and, under proinflammatory conditions, by infiltrating lymphocytes could support NE cell differentiation and play a role in NE differentiation processes of tumor cells in hormone-refractory prostate cancer.     

Neuroendocrine differentiation in carcinomas of the prostate: Do neuroendocrine serum markers reflect immunohistochemical findings?

The aim of the present study was to examine the correlation between the immunohistochemical findings and the serum markers for neuroendocrine (NE) cells in patients with carcinoma of the prostate. Preoperative serum values of chromogranin A (CgA), chromogranin B (CgB), pancreastatin (Pst), neuron-specific enolase (NSE), and prostatic specific antigen (PSA) were determined in 22 patients. The tissue specimens were obtained by a palliative transurethral resection of the prostate (TURP) because of urinary outflow obstruction. Immunohistochemistry was performed by using antibodies against CgA, CgB, NSE, serotonin, thyroid-stimulating hormone (TSH), and somatostatin. Tumor cells with NE differentiation were found in 91% of the cases. No patient had elevated serum values of NSE, despite the presence of NSE-positive tumor cells in 77% of the tumors. Neither did CgB in serum correlate with the immunohistochemical findings. Elevated serum values of CgA were found in 59% of patients. A positive correlation between the number of CgA-staining cells and the serum values of CgA was found, as seven out of eight patients with groups of CgA-positive tumor cells had elevated serum values of CgA. We conclude that CgA, in contrast to NSE, CgB, and Pst, seems to be a useful serum marker in predicting the extent of NE differentiation in prostatic tumors. Prostate 30:1–6, 1997 © 1997 Wiley-Liss, Inc.     

Comparison of the zones of the human prostate with the seminal vesicle: morphology, immunohistochemistry, and cell kinetics

BACKGROUND: The prostate contains three glandular zones (central, peripheral, transition) with widely differing susceptibilities to cancer and benign prostatic hyperplasia (BPH). Most of the prostate is derived from urogenital sinus, but the central zone may be derived from Wolffian duct, in common with the seminal vesicles (SV). The peripheral zone is the most frequent site of cancer and the transition zone is the almost exclusive site of BPH. METHOD: We compared the histology and immunohistochemistry of the SV with those of the prostate zones in order to identify differences associated with susceptibility to disease or different embryological origins. Sections from the prostates of nine organ donors (aged 15-36) were stained for tissue-specific markers, antigens previously shown to stain differentially between the zones and markers of cell proliferation and cell death. RESULTS: Neuroendocrine cells were absent from the SV and significantly fewer neuroendocrine cells were seen in the central zone compared to the peripheral zone. Most of the SV epithelium stained for lactoferrin, compared to approximately one-third of central zone and only 2% of peripheral zone epithelial cells. The proliferative index of the central zone was approximately 50% lower and the incidence of apoptotic cells approximately half that of the peripheral and transition zones. CONCLUSIONS: The central zone has features in common with both the SV and the other zones of the prostate. The higher incidence of proliferative diseases in the transition and peripheral zones may be associated with the higher rate of cell turnover observed in these zones.     

Localization of protein gene product 9.5 immunoreactivity in derivatives of the human Wolffian duct and in prostate cancer

BACKGROUND: Protein gene product 9.5 (PGP 9.5) has been considered to be a neuronal marker, but it is also present in extraneuronal tissues, e.g., the human mammary gland and rat epididymis. Its presence and distribution in the developing and adult male human genital tract have been unknown. METHODS: Immunohistochemical reactions were performed on human embryonic and postnatal specimens of the male genital tract, using commercial monoclonal and polyclonal antibodies. RESULTS: PGP 9.5 immunoreactivity was found in the Wolffian duct of human embryos (55-85 mm crown-rump length). Strong reactivity was observed in mesonephric tubular cells and at the apical rim of Wolffian duct cells. Owing to their PGP 9.5 immunoreactivity, these cells could also be identified on the surface of the embryonic verumontanum, extending from the orifices of the Wolffian duct to a small stretch of the urogenital sinus. There they contrasted sharply against non-Wolffian cells. In the adult human genital tract, PGP 9.5 immunoreactive material was present in the supranuclear portion of some epithelial cells of the epididymal efferent ductules, in isolated cells of the ejaculatory ducts, and in prostate cancer specimens. In the ejaculatory ducts, the PGP 9.5-immunoreactive cells were free of immunoreactivity for semenogelin, the major secretory product of the ejaculatory-vesicular-ampullary complex, and they also lacked chromogranin A-immunoreactivity. In prostate cancer specimens, PGP 9.5 immunoreactivity was never observed in secretory cells (immunoreactive for prostate-specific antigen), but was restricted to neuroendocrine cells, where it occurred either alone or coexpressed with chromogranin A-immunoreactivity. CONCLUSIONS: PGP 9.5-immunoreactivity is prenatally distributed in the Wolffian duct and its derivations; postnatally, it is restricted to a few cells derived from the initial and terminal segment of the Wolffian duct, and to neuroendocrine cells in prostate cancer specimens.     

2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits prostatic epithelial bud formation by acting directly on the urogenital sinus

PURPOSE: In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure causes lobe specific inhibition of prostate development in C57BL/6 mice due primarily to region specific inhibition of prostatic epithelial bud formation by the urogenital sinus (UGS). This inhibition requires that the receptor for TCDD, the aryl hydrocarbon receptor (AhR), must be present. We tested the hypothesis that TCDD inhibits prostatic epithelial bud formation by acting directly on the UGS. MATERIALS AND METHODS: UGSs were removed from WT and AhR null mutant (AhRKO) male C57BL/6 mice on gestation day 14 and incubated in vitro with vehicle, 10-8 M testosterone or 10-8 M testosterone plus 10-9 M TCDD for 5 days. Budding was evaluated by a newly developed technique, namely scanning electron microscopy of UGS epithelium after removal of UGS mesenchyme. RESULTS: Few buds were present in UGSs of either genotype in the absence of testosterone, while many were observed when testosterone was present. TCDD prevented prostatic epithelial buds from forming in UGSs from WT mice but it had no effect on UGSs from AhRKO mice. CONCLUSIONS: TCDD can act directly on the UGS to cause AhR dependent inhibition of prostatic epithelial bud formation. Because this inhibition occurred at a TCDD concentration similar to the estimated concentration at which TCDD inhibits bud formation in vivo, it appears that TCDD inhibits prostatic budding primarily via direct effects on the UGS rather than indirectly through effects on other organs.     

Neuroendocrine cells and nerves in the prostate of the guinea pig: effects of peripheral denervation and castration

BACKGROUND: Neuroendocrine (NE) cells and nerves in the prostate gland are thought to play a central role in the regulation of growth, cellular differentiation and homeostasis of secretory activity. The objective of this experimental study was to describe the effects of peripheral denervation and castration on NE cells and nerves in the guinea pig prostate. METHODS: Guinea pigs underwent sham-operation, unilateral and bilateral hypogastric nerve resection, extirpation of the right anterior major pelvic ganglion (AMPG), autotransplantation of prostatic tissue and castration. Cryostat sections of prostatic tissue were examined with immunohistochemistry by using serotonin (5-HT) and chromogranin A (CgA) and various neuropeptides. RESULTS: The number of 5-HT-IR NE cells was four-fold higher than CgA-IR NE cells. The innervation pattern was uniform throughout the gland with subepithelial nerves in close proximity to NE cells. Autotransplants of prostatic tissue showed total loss of nerves, but the number and morphology of 5-HT-IR NE cells were unaltered. Extirpation of the right AMPG showed significant reduction in prostate weight, decreased density of nerve terminals in the superior part of the ipsilateral prostate, whereas the number and morphological feature of 5-HT-IR NE cells remained unaffected in the entire prostate. Castration induced atrophy of the gland with a significant reduction in weight (unpaired t-test, P < 0.001), but without effect upon 5-HT-IR NE cells. CONCLUSIONS: The guinea pig seems to be a useful animal model for studies on the role of the NE cells in the prostate. NE cells seem to be independent of innervation and androgens. It seems that other factors influence the NE cell population to a greater extent.     

尿生殖窦植入致大鼠良性前列腺增生的组织形态学研究

目的:采用尿生殖窦植入法建立大鼠良性前列腺增生模型并进行组织形态学半定量及免疫组化研究。方法:7周龄雄性SD大鼠32只,随机分为4组:假手术对照组,尿生殖窦模型2周组,尿生殖窦模型3周组,尿生殖窦模型6周组。尿生殖窦植入各模型组大鼠,分别饲养指定周期后,分离各组大鼠前列腺组织,测量湿重及体积,右侧前列腺腹前叶切片并进行半定量组织形态学测量,采用免疫组化法检测上皮、间质、平滑肌中相关表达因子。结果:各模型组大鼠右侧前列腺腹叶湿重及指数、体积及指数随模型培养时间延长而增加(P<0.05),间质面积比例、间质相对总体积随时间延长显著增加(P<0.01),3周模型组的间质平均比例高达75.32%;模型组上皮相对总体积随时间延长亦增加。与假手术对照组相比,腺腔面积、上皮面积比例,腺腔面积比例减少。广谱细胞角蛋白免疫组化染色阳性颗粒定位于上皮细胞,波形蛋白于间质细胞丰富表达,平滑肌肌动蛋白于腺腔周围表达。结论:大鼠尿生殖窦良性前列腺增生模型以间质增生为主,相关因子表达部位与人类良性前列腺增生相似。