Potentiating Effect of Buserelin Acetate, an LHRH Agonist, on the Proliferation of Ventral Prostatic Epithelial Cells in Testosterone-Treated Castrated Rats

Background: We used buserelin acetate ([D-Ser(But)6] LHRH), an LHRH agonist and strong blocker of LH secretion, as a treatment for prostatic cancer. It is possible that this LHRH agonist has a proliferative effect on the prostate in addition to suppressing LH secretion. The purpose of this study was to examine the proliferative effect of LHRH agonist on rat prostatic epithelial cells.
Methods: We determined the optimal dose of testosterone necessary to maintain a positive level of proliferating cell nuclear antigen (PCNA) in the ventral prostatic epithelial cells of castrated Wistar rats. Testosterone-treated rats then received various doses of buserelin acetate. Castrated rats without exogenous testosterone also received buserelin acetate. The PCNA positivity was determined by immunohistochemistry with anti-PCNA monoclonal antibody.
Results: The optimal dose of testosterone enanthate was 4mg at 0 and 28 days after castration. Administration of buserelin acetate on day 0 and 28 in doses of 0.1 6mg to 1.28mg significantly increased PCNA positivity in a dose-dependent manner. Administration of buserelin acetate to castrated rats without testosterone also increased PCNA positivity but there was no statistical significance. Conclusions: Buserelin acetate has a potentiating effect on the proliferation of ventral prostatic epithelial cells of castrated rat in the presence of a physiological level of exogenous testosterone. This effect may slightly influence the result of hormonal therapy by LHRH agonist.     

Engineered FGF-2 expression induces glandular epithelial hyperplasia in the murine prostatic dorsal lobe

OBJECTIVE: It is known that androgens and stromal-epithelial interactions are required for the formation and growth of the prostate. FGF-2 is overexpressed in prostatic stromal cells in benign prostatic hypertrophy (BPH)/prostate cancer. This supports the paracrine/autocrine growth of prostatic epithelial/stromal cells in the pathogenesis of BPH and invasive prostate cancer. METHODS: We established transgenic mice expressing FGF-2 under the control of a short rat probasin promotor. FGF-2 transgenic founder mice expressing FGF-2 in the prostate were infertile. Thus, male founder mice were sacrificed for histological analysis. RESULTS: FGF-2 was expressed in epithelial cells in glands of the dorsal, lateral, and ventral prostatic lobes of two FGF-2 transgenic founder mice, but not in the anterior lobe of transgenic mice or in any lobe of non-transgenic control littermates. Acinar epithelial glands in dorsal prostatic lobes of FGF-2 transgenic mice expressing FGF-2 were more dense and showed simple papillary hyperplasia of epithelial cells compared with those of control littermate mice. Glandular and luminal enlargement without epithelial growth was observed in the ventral lobe of FGF-2 transgenic mice compared with the controls. CONCLUSION: In conclusion, FGF-2 transgenic mice under the control of rat probasin promoter showed simple epithelial hyperplasia in glands of the prostatic dorsal lobe and glandular enlargement without epithelial growth in the prostatic ventral lobe.     

缺氧诱导因子-1α在去势前后大鼠腹叶前列腺中表达的变化

目的探讨与缺氧相关的缺氧诱导因子-1α(HIF-1α)是否参与去势后前列腺萎缩过程.方法24只SD大鼠分为3组,其中A组(n=8)为假手术对照组,B组(n=8)为去势组,C组(n=8)为雄激素替代组(去势后肌注十一酸睾酮50mg/kg);术后3天处死,通过半定量RT-PCR检测与HIF-1α在去势前后前列腺表达变化.结果去势后大鼠前列腺的体积萎缩变小;雄激素替代组出现前列腺增生变大;对照组正常的大鼠前列腺有HIF-1 α mRNA低水平表达,去势组HIF-1α mRNA表达量增加,雄激素替代组HIF-1αmRNA表达量减少,与正常对照组比较,去势组的HIF-1α mRNA的表达量显著增加(P＜0.05),雄激素替代组的HIF-1αmRNA的表达量显著减少(P＜0.01).结论前列腺组织的缺氧参与去势后大鼠前列腺的早期萎缩过程.     

Induction of metallothionein by CdCl2 administration in rat prostate

Metallothionein (MT) induction in the rat prostate gland was investigated by means of cadmium chloride administration. Ten-week-old male Wistar rats housed with cadmium free food were divided into three groups of six rats each and castrated. After seven days, 1 mg of testosterone propionate per rat was injected subcutaneously once a day until the end of the experiment. After three weeks, rats were injected daily for six days with a physiological saline, 0.3 mg/kg CdCl₂, and 0.9 mg/kg CdCl₂. MT concentration of the ventral and dorsal lobes was significantly increased in the three groups in proportion to the dose of CdCl₂. MT content of the lateral lobe in three groups was also increased, but was not significantly different. Immunohistochemically, MT was induced mainly in the ventral lobe in the basal cells, and in the lateral and dorsal lobes in the epithelial cells. The weights of the prostatic lobes were similar in the three groups, and no histological change was identified. These results suggested that MT in the prostate was induced by cadmium administration, and that it may prevent cellular damage from harmful metals. © 1993 Wiley-Liss, Inc.     

Pumpkin seed oil and phytosterol-F can block testosterone/prazosin-induced prostate growth in rats

INTRODUCTION: This study was undertaken to investigate the effects of pumpkin seed oil alone or combined with Phytosterol-F on testosterone/prazosin-induced (T-P) prostate growth in rats. MATERIALS AND METHODS: Forty adult Wistar rats were divided into five groups, including: one control group, rats treated with vehicle only, one group treated with T-P, and two groups of T-P-treated rats, one receiving orally pumpkin seed oil alone and one group receiving orally pumpkin seed oil combined with Phytosterol-F. Two weeks later, the prostatic weight-to-body weight ratio was determined after sacrifice. The total protein concentration was measured by using a protein assay. Some ventral prostatic tissues were histologically examined after hematoxylin-eosin staining. RESULTS: Histological sections of the ventral prostate showed that the architecture of the prostate glands became hyperplastic in the T-P rats, but not in the control or vehicle-treated animals. As compared with the control or vehicle group, T-P rats had a significantly higher prostatic weight-to-body weight ratio for the ventral prostate (p=0.05 and p=0.007, respectively), but not for the dorsolateral prostate (p=0.53 and p=0.73, respectively). The T-P rats had significantly higher protein levels within both lobes (ventral lobe, p=0.02 and p<0.0001, respectively; dorsolateral lobe, p=0.06 and p=0.005, respectively). As compared with the T-P-alone rats, the TP rats treated with pumpkin seed oil alone or pumpkin seed oil combined with Phytosterol-F had a significantly lower weight ratio for the ventral prostate (p=0.01 and p=0.004, respectively) and significantly lower protein levels within both lobes (p=0.03 and p=0.003, respectively; p=0.007 and p=0.002, respectively). In addition, Phytosterol-F had some additive effect on the total protein synthesis within the ventral prostate (p=0.02). CONCLUSION: Pumpkin seed oil alone or combined with Phytosterol-F can block the T-P-induced increases in prostatic weight-to-body weight ratio and protein synthesis.     

消癃通闭对大鼠前列腺组织碱性成纤细胞生长因子表达的影响

目的：了解中药消癃通闭对前列腺组织碱性成纤维细胞生长因子（ＢａｓｉｃＦｉｂｒｏｂｌａｓｔＧｒａｏｔｈＦａｃｔｏｒ,ｂＦＧＦ）表达的影响。方法：以去势Ｗｉｓｔａｒ大鼠,经皮下每天注射睾酮,同时给予中药消癃通闭药粉灌胃,２０ｄ时断髓处死。取相同部位前列腺腹叶,以免疫组化定量技术对前列腺组织ｂＦＧＦ进行测试。结果：消癃通闭高剂量组的ｂＦＧＦ表达明显低于睾酮组,Ｐ＜００１;并发现ｂＦＧＦ的表达主要位于腺上皮细胞的胞浆,而胞核及间质部分表达较少。结论：中药消癃通闭治疗前列腺增生的机理之一是该药明显抑制了前列腺组织中的ｂＦＧＦ的表达,进而抑制了前列腺细胞的生长     

Superoxide dismutase in the prostate lobes of aging Brown Norway rats

BACKGROUND: Spontaneous age-dependent epithelial cell hyperplasia occurs in the lateral and dorsal, but not the ventral, lobes of aging Brown Norway (BN) rats. Diminished antioxidant enzyme activities and increased formation of reactive oxygen species (ROS) promote the pathology of many aging disorders. We investigated the hypothesis that prostatic epithelial cell hyperplasia in the BN rat was related to age-dependent and/or lobe-specific changes in superoxide dismutase (SOD). MATERIALS AND METHODS: Using Western blots, immunohistochemistry and enzyme activity assays we determined the levels of protein expression, subcellular localization, and activities, respectively, of the three SOD isoforms, cytoplasmic SOD1, mitochondrial SOD2, and extracellular SOD3 in the ventral, lateral, and dorsal prostate lobes of 4-month-old rats with normal prostate morphology, in 24-month-old rats with lobe-specific hyperplasia and in older 30-month-old rats. RESULTS: We observed little change in SOD activities as a function of age, although expression of SOD3 increased in the prostatic lobes of older rats. SOD2 levels were higher in the lateral lobe of 4- and 24-month-old rats, but declined by 30 months of age to levels in the ventral and dorsal lobes. SOD1 was localized by immunohistochemistry to the nuclei of epithelial cells in all lobes, but the number of immunopositive nuclei increased in the lateral and dorsal lobes of 24-month-old animals. The concentration of zinc was highest in the prostate lobes of 24-month-old animals. CONCLUSION: Based upon our data, superoxide dismutase is not significantly altered in the rat prostate during aging and thus is unlikely to be an important factor in the evolution of epithelial cell hyperplasia.     

Effect of prenatal vitamin D (calcitriol) exposure on the growth and development of the prostate.

BACKGROUND: We previously found that in the absence of testosterone (T), calcitriol promotes proliferation of normal prostatic stroma, while in the presence of T, it has a differentiating effect on prostatic epithelium. The present study was conducted to determine the effect of calcitriol exposure in utero on the postnatal development of the normal prostate. METHODS: Pregnant rats were injected subcutaneously with either 1.25 microg of calcitriol or vehicle alone on alternate days till delivery. Calcitriol-exposed and control pups were sacrificed at age 25 days (prepuberty), 63 days (postpuberty), or 102 days (adults), and their prostates and seminal vesicles were harvested and weighed. RESULTS: Pups prenatally exposed to calcitriol and sacrificed before puberty (25 days) had a 35% greater mean prostatic weight than controls (0.0314 vs. 0.0422 g, P < 0.007), and calcitriol-exposed adult rats (102 days) had a 68% greater mean prostatic weight than controls (0.1365 vs. 0.2304 g, P < 0.005). No differences were observed in seminal vesicle weights, and in serum calcium and testosterone levels. A disproportionately high mortality rate from sudden death (71%) was observed at puberty in uncastrated male rats prenatally exposed to calcitriol. CONCLUSIONS: These findings suggest that high-dose calcitriol exposure in utero may uniquely influence subsequent prostatic growth. Nonandrogenic steroids such as calcitriol may also be involved in genetic imprinting of the prostate.     

Effects of finasteride and bicalutamide on prostatic blood flow in the rat

OBJECTIVE: To determine whether finasteride and bicalutamide, both currently used in the clinical management of patients with prostate diseases because they have anti-androgenic properties, have any effects on prostatic blood flow in a rat prostate model, as androgens are known to be involved in the regulation of prostatic blood flow and angiogenesis. MATERIALS AND METHODS: Both finasteride and bicalutamide were supplied as oral suspensions in water and given daily to rats for 7 days by tube feeding. Blood flows to the ventral and dorsal prostates, and to the kidneys, were measured using the radioactive microsphere technique. In the bicalutamide experiments, some rats were treated with the Leydig cell toxin ethane dimethane sulphonate (EDS), to obtain a castration-like effect, and one group of these rats received testosterone. RESULTS: Finasteride induced a clear decrease in blood flow to the ventral and dorsal prostates after 7 days of treatment, with no significant changes in blood pressure or kidney blood flow. Bicalutamide inhibited the testosterone-induced increment of prostatic blood flow observed in EDS-treated animals. CONCLUSIONS: Finasteride, a blocker of 5alpha-reductase, decreases prostate blood flow after 7 days of administration. The response was slower than that after castration, but was of similar magnitude. Blood flow was also decreased after treatment with the androgen-receptor inhibitor bicalutamide. These observations suggest that prostatic blood flow is increased by dihydrotestosterone, and that the androgen receptor is responsible for mediating this effect.     

Cadmium chloride-induced dysplastic changes in the ventral rat prostate: an immunohistochemical and quantitative study

BACKGROUND: Cadmium chloride is an environmental toxic that might be implicated in human prostate carcinogenesis. The study was directed: 1) to evaluate the immunoexpression of markers for cell proliferation, apoptosis, and resistance to apoptosis, and 2) to estimate the size of premalignant cell population in the preneoplastic changes induced in ventral prostates of rats treated with cadmium chloride administered in drinking water. METHODS: The following parameters were calculated in the ventral prostatic lobe of normal rats and rats that received cadmium in drinking water during 18 months: total volume, epithelial volume, total number of epithelial cells, numerical density of epithelial cells, percentage of cells that immunostained to the proliferating cell nuclear antigen (PCNA), percentage of apoptotic cells (evaluated by a DNA fragmentation method), and absolute volume and volume fraction of immunostaining to bcl-2. RESULTS: The percentage of PCNA immunoreactive nuclei, the bcl-2 expression, and the numerical density of epithelial cells were significantly (P < 0.05) increased in the dysplastic prostatic acini of treated rats in comparison with the normal acini of treated rats and control animals. The percentage of apoptotic nuclei from ventral dysplastic acini was significantly (P < 0.05) decreased in comparison with that of normal acini. A negative correlation between proliferation and apoptosis was found in dysplastic lesions. CONCLUSIONS: Prostate epithelial dysplasia induced in rats by cadmium presents an increased proliferative activity and high expression of bcl-2 protein, as was described in human prostate intraepithelial neoplasia. However, the rate of apoptosis in rat dysplasia was importantly decreased, in contrast to that observed in some human preneoplastic changes. This decrease might be related to the increase of bcl-2 expression.     

Induction of proliferative lesions of ventral prostate, seminal vesicle, and other accessory sex glands in rats by N-methyl-N-nitrosourea: effect of castration, pretreatment with cyproterone acetate and testosterone propionate and rat strain.

Wistar (Cpb:WU), F344 or Sprague-Dawley rats were sequentially treated with cyproterone acetate (CA) for 21 days, testosterone propionate (TP) for 3 days, followed by a single i.v. injection of N-methyl-N-nitrosourea (MNU). One group of Wistar rats was castrated 4 weeks after MNU injection, and another group 58 weeks after MNU, when the first prostatic carcinoma was detected. Control groups received only CA + TP, CA, MNU, or they remained untreated. Early or late castration inhibited the development of atypical hyperplasia of the ventral prostate in Wistar rats. This lesion was induced by the CA + TP + MNU treatment in F344 rats, but not Sprague-Dawley rats; in Wistar rats, it was induced by CA + TP treatment, irrespective of whether MNU was given. Hypertrophic-hyperplastic lesions of the seminal vesicle were induced by MNU, irrespective of pretreatment, and their development was prevented by early castration and inhibited by late orchiectomy. Dorsolateral prostate carcinomas and preneoplasia occurred only in low incidence in Wistar and Sprague-Dawley rats. These lesions were absent in F344 rats that had received treatment with CA + TP + MNU. No dorsolateral prostate (pre)neoplasia was found in Wistar rats subjected to early orchiectomy, but rats castrated at 58 weeks had an incidence similar to that for the intact group treated with CA + TP + MNU. This finding supports the contention that androgens are required for the development of MNU-induced prostatic cancer in rats but that advanced carcinomas are androgen insensitive. Differences in incidence and localization of prostatic proliferative lesions between F344 and Wistar rats and between dorsolateral and ventral prostate could not be explained by differences in epithelial cell proliferative responses to CA + TP treatment at the time of MNU injection, since they were similar in ventral and dorsolateral prostate and were more prominent in F344 rats than in Wistar rats. DNA damage as estimated by MNU-induced unscheduled DNA synthesis also did not differ between dorsolateral and ventral prostate.     

Androgen-supported estrogen-enhanced epithelial proliferation in the prostates of intact Noble rats

Using a stathmokinetic in vivo metaphase-arrest technique, we studied cell proliferation and histological changes in the ventral (VP) and dorsolateral (DLP) prostate lobes of intact Noble (Nb) rats following a 16 week treatment with testosterone (T) or 5 alpha-dihydrotestosterone (DHT) administered separately or in combination with various estrogens. The combined treatment of rats with T and either estradiol-17 beta, estradiol-17 alpha, or moxestrol induced florid dysplasia and markedly elevated the mitotic index (MI) in affected regions of the DLP. In contrast, joint DHT and estrogen treatment caused only mild proliferative lesions in this lobe. The separate administration of either androgens or estrogens suppressed epithelial proliferation in both the VP and DLP, but they differed in their histological effects on these tissues. Thus DHT or T alone maintained the morphological integrity of VP and DLP, whereas E2-17 beta or moxestrol caused massive atrophy of both lobes. Although dysplastic foci were randomly scattered throughout the DLP, the most dramatic lesions occurred in periurethral ducts. With the exception of joint T and E2-17 alpha treatment, which induced proliferative alterations in the VP, dysplasia was always restricted to the DLP of all animals receiving both androgens and estrogens. Concomitant comparative stathmokinetic studies of the prostates of T-treated castrates suggest that protracted androgen-supported estrogen stimulation of the DLP is necessary to overcome factors that normally limit cell proliferation.     

Differential effects of growth factor antagonists on neoplastic and normal prostatic cells

Growth factors such as epidermal growth factor and fibroblast growth factor have been suggested to be involved as paracrine or autocrine mediators of androgen action in normal and malignant prostatic cells. Suramin and protamine are potent in vitro growth factor antagonists. To evaluate the effect of growth factor antagonists on prostatic growth, suramin and protamine were administered to castrated rats simultaneously receiving exogenous testosterone replacement in an attempt to block androgen-dependent restoration of the normal rat ventral prostate. Using this prostatic restoration model, there was no statistical difference in the prostate wet weight or total DNA content attained between rats given testosterone alone and those given testosterone in combination with either suramin or protamine. In intact rats, suramin administration caused an 80% reduction in serum testosterone; concomitantly, these rats had a 40% reduction in mean prostate weight. This decrease in size could be blocked with androgen supplementation. To examine the effects of growth factor antagonists on neoplastic prostatic cell growth, rats bearing the androgen-independent AT-2 subline of the Dunning R-3327 tumor were treated with either suramin or protamine. The same dosing regimen found to be ineffective in blocking the restoration of the involuted prostate of castrated rats resulted in a significant reduction in the growth rate of AT-2 tumors. These results suggest that the growth factor antagonists suramin and protamine given in vivo have a differential ability to slow the growth of malignant vs. normal prostatic cells.     

Regional variations in the testicular dependence of prolactin binding and its possible relationship to castration-induced involution in rat prostate gland

Prolactin binding sites of ventral, lateral, and dorsal lobes of rat prostate were examined immunohistochemically 1, 2, 4, and 8 days after castration or sham operation. In sham-operated rats each lobe exhibited a distinct pattern of intracellular and intraluminal prolactin binding. A loss in prolactin binding from epithelial cells of ventral prostate, which was visualized postcastration, was quantitated with the aid of an image analyzer and then statistically evaluated. The proportion of ventral prostate epithelial cells devoid of prolactin binding increased from approximately 13% in sham-operated rats to approximately 29% 1 day after castration, and reached a peak level of about 71% 4 days postcastration. No loss of prolactin binding was evident in either lateral or dorsal prostate up to 8 days postcastration. Direct measurement of epithelial cell heights and subsequent statistical evaluation revealed similar regional differences in the rates and extent of prostate involution. Eight days after castration ventral prostate epithelial cell heights decreased by 56% whereas lateral and dorsal lobe epithelial cells heights decreased about 25% and 14%, respectively. The apparent relationship between testicular dependence of prostatic prolactin binding and castration-induced prostatic involution are discussed in terms of possible regional variations in the prolactin-androgen interplay in prostate.     

雄激素对大鼠腹叶前列腺GDNF mRNA表达的影响

目的 :探讨雄激素对大鼠腹叶前列腺中胶质细胞源性神经营养因子 (GDNF)mRNA表达的影响。　方法 :2 4只SD大鼠分为 3组 ,其中A组 (n =8)为假手术对照组 ,B组 (n =8)为去势组 ,C组 (n =8)为雄激素替代组 (去势后肌注十一酸睾酮 5 0mg/kg) ;术后 3d处死 ,通过半定量RT PCR检测GDNFmRNA在去势前后和雄激素替代组大鼠腹叶前列腺中的表达变化。　结果 :去势后大鼠前列腺的体积萎缩变小 ;雄激素替代组出现前列腺增生变大 ;对照组正常的大鼠前列腺有GDNFmRNA表达 ,去势组GDNFmRNA表达量减少 ,雄激素替代组GDNFmRNA表达量增加。与正常对照组比较 ,去势组的GDNFmRNA表达量显著减少 (P <0 .0 5 ) ,雄激素替代组的GDNFmRNA表达量显著增加(P <0 .0 5 )。　结论 :雄激素可增加GDNFmRNA表达 ,促进前列腺细胞生长。     

Effects of Melandrium firmum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats

Benign prostatic hyperplasia (BPH) is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents that can cause severe side effects, plant extracts are frequently used to treat BPH. In this study, we investigated whether the Melandrium firmum methanolic extract (MFME) improves BPH, using the testosterone propionate (TP)-induced BPH rat model. Castration was performed via the scrotal route under sodium pentobarbital anaesthesia. BPH in castrated rats was generated via daily subcutaneous injections of TP (3 mg kg(-1)) dissolved in corn oil, for 4 weeks. MFME was administered daily by oral gavage at a dose of 200 mg kg(-1) for 4 weeks, along with the TP injections. The control group received injections of corn oil subcutaneously. At the scheduled termination of the experiment, all rats were killed and their prostates weighed; the relative prostate weight (prostate/body weight ratio) was calculated, and histomorphological changes in the prostate were examined. Additionally, we measured the levels of testosterone and dihydrotestosterone (DHT) in the serum and the prostate. Experimentally induced BPH led to marked decreases in the relative prostate weight and the DHT levels in the serum and the prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and MFME treatment suppressed the severity of the lesions. These results indicate that MFME effectively inhibits the development of BPH induced by testosterone in a rat model. Further studies will be needed to identify the compound(s) responsibility for inducing the protective effect against BPH and determine its mechanism of action.     

他莫昔酚对大鼠前列腺增生动物模型的抑制作用及机理研究

目的 :探讨他莫昔酚抑制前列腺增生的作用机理。　方法 :将Wistar成年大鼠肌肉注射丙酸睾丸酮 ,同时以他莫昔酚常规灌胃。于给药 7、15、30d时分批处死大鼠 ,称取前列腺重量 ,标本做常规病理切片 ,电镜观察前列腺组织细胞结构变化。　结果 :给药 7d时单用睾酮组前列腺指数高于对照组 ,也高于灌胃组。剩余大鼠分 2组 ,其中 1组继续单用他莫昔酚灌胃 ,于第 15、30d时分组处死剩余大鼠。光镜染色观察及电镜扫描均证实他莫昔酚组前列腺上皮细胞及基质的增殖被抑制。　结论 :他莫昔酚通过对雌激素的拮抗作用 ,阻断雌激素在前列腺增生中的作用 ,从而抑制前列腺增生。     

Experimental cryptorchidism inhibited growth of the rat ventral prostate

Adult Sprague-Dawley male rats, weighing about 350 g, were rendered cryptorchid by suturing the testes to the lateral abdominal wall. Twenty-eight days later, cryptorchidism resulted in a significant decline in testis weight and suppressed spermatogenesis. The ventral prostate was significantly smaller in cryptorchid rats. There was no significant difference in serum testosterone levels between the normal and cryptorchid rats. Charcoal-stripped aqueous extracts of the testis from intact and cryptorchid animals were tested on primary cultures of rat prostatic stromal cells. Cultures treated with extract from the intact testis had a significantly increased cell proliferation as assessed by cell count and by the rate of 3H-thymidine incorporation. Additionally, extracts of seminiferous tubules significantly increased prostate stromal cell proliferation compared to extracts of testicular interstitial components. Furthermore, this proliferative effect of testicular extracts is specific to the prostate as extract of both normal and cryptorchid testis stimulated proliferation of rat footsole fibroblasts in culture, but only extracts from intact testis stimulated proliferation of prostate stromal cells. These observations demonstrate that the testis produces nonandrogenic substances that can promote growth of prostatic stromal cells and that these substances were eliminated in the cryptorchid testis.