去势Beagle犬前列腺增生模型的建立

目的 :利用Beagle犬建立前列腺增生模型。　方法 :2年龄雄性Beagle犬 2 4只 ,随机分成对照组和 3个剂量的实验组共 4组 ,每组 6只 ,去势 2个月后 ,肌注给药。实验组分别给予丙酸睾酮 (TP) 0 .8、2 .5、7.5mg/kg ,对照组给予等体积溶剂。 2个月后 ,处死 12只动物 ,取前列腺组织 ,称重测量体积 ,放免法测定血清及前列腺组织中双氢睾酮 (DHT)水平 ,组织切片观察前列腺腺腔面积及腺上皮细胞高度。B超测量去势前、后 2个月及给予TP 2个月时犬前列腺体积。　结果 :B超结果显示 ,去势 2个月后 ,各组犬前列腺体积较去势前均明显缩小 (P均 <0 .0 1) ;给予TP 2个月后 ,各实验组犬前列腺体积明显大于对照组 (P均 <0 .0 1)。各实验组犬前列腺湿重及实际体积与对照组相比 ,均明显增重增大 (P均 <0 .0 5 ) ,并存在剂量依赖关系。犬血清及前列腺中DHT含量随TP剂量的增大而增加。显微图像分析结果显示 ,犬前列腺腺腔面积随TP剂量增大而增加 ,腺上皮细胞高度也随TP剂量增大而增高。　结论 :给予去势Beagle犬TP 2个月后 ,可成功建立前列腺增生模型。     

Comparison of the effects of new specific azasteroid inhibitors of steroid 5α-reductase on canine hyperplastic prostate: Suppression of prostatic DHT correlated with prostate regression

Four new azasteroid inhibitors of steroid 5α-reductase were compared to the benchmark compound finasteride, each at a dose level of 1 mg/kg/day, as well to placebo and to castration, in seven groups of mature male beagle dogs with enlarged prostates. Prostate volumes were measured repetitively by a volume MRI method over 15 weeks of treatment. The study probed the obverse of the familiar relation between DHT and prostate growth, and provides the first documentation of a tight negative correlation between prostate regression and the prostatic concentration of DHT across a range of treatment regimens (r = ?0.982). In this first direct comparison study of structure vs. in vivo activity for several azasteroids in the dog model of BPH, relative efficacy for induction of shrinkage of the dog prostate did not correlate at all with the inhibitor's relative activity against the dog 5α-reductase in vitro. On the basis of the relative IC₅₀ values it would not have been predicted that, at the dose tested, the analogue MK-434 (17β-benzoyl-4-aza-5α-androst-1-en-3-one) was distinguished from the other inhibitors with respect to the induction of faster and more complete regression (69%) as well as greater reduction in prostatic DHT (95%), both of which approached the castrated dog levels of 75% prostatic shrinkage and >98% reduction in DHT. Treatment with any one of the five azasteroids induced two- to five-fold increases in prostatic testosterone. However, total androgen was conserved at the placebo control level. Despite the differences noted, each azasteroid tested induced a highly significant decrease in prostatic volume that correlated tightly with a decreased prostatic DHT level in canine spontaneous BPH.     

Androgen and prostatic stroma

Aim: To investigate the effect of androgen on the proliferation, differentiation and regression of canine prostatic stromal cells in vivo and human stromal cells in vitro. Methods: Twenty-two dogs, including 15 normal prostate dogs and 7 prostatic hyperplasia dogs, had their serum concentration of testosterone and estrodiol determined by radioimmunoassay before and after castration. The expression of androgen receptor (AR) and estrogen receptor (ER) in the prostate were analysed by immunohistochemistry and semi-quantitative RT-PCR before and after castration. Light microscopy, transmission electron microscopy and TUNEL assay were carried out successively before and after castration to evaluate the prostatic histomorphology. In vitro serum-free cell cultures from human prostatic stroma were established and exposed to dihydrotestosterone (DHT). The proliferation of the cell culture was detected by MTT assay. The expression of TGFβ, bFGF, AR, and smooth muscle cell (SMC) specific proteins (myosin and/or sm     

Cell kinetics and differentiation after hormonal-induced prostatic hyperplasia in the dog

BACKGROUND: Our aim was to characterize the immunophenotypical changes in canine prostate epithelium after hormonal-induced benign prostatic hyperplasia (BPH). METHODS: Castrated dogs (aged 1-2 and 9-12 years) were treated with vehicle (group C), androstanediol (group A), or androstanediol plus estradiol (group AE). Surgical prostate biopsies were obtained before and after castration and after hormonal treatment. Tissue sections were stained using antibodies specific for basal cells (34betaE12), transiently proliferating (TP)/amplifying cells (RCK103), and luminal exocrine cells (RGE53). RESULTS: Castration resulted in a marked reduction in specific immunoreactivity associated with luminal secretory cells and basal cells in young dogs. In older dogs the number of basal cells remained constant. Hormonal treatment (AE) resulted in an increased number of cells with an immunophenotype that was associated with the TP/amplifying cell compartment and hyperplastic luminal epithelium. CONCLUSIONS: The relative increase in TP/amplifying cells in hormonally induced BPH in the dog is in line with a stem-cell-derived proliferation. Moreover, the finding of androgen-independent basal cells in the prostate of older dogs may contribute to the enhanced risk of development of BPH with increasing age.     

四黄前列片对尿生殖窦植入法小鼠前列腺增生模型的影响

目的 探讨阴黄前列片对小鼠前列腺增生模型的影响。方法 选用NIH系雄性小鼠，依文献方法，行前列腺腹叶内植入尿生殖实组织，制备BPH动物模型，给药30d后处死动物，取前列腺组织，称重测量体积，组织切片观察前列腺腺腔嘶积和腺上皮高度，用免疫组化法研究实验各组前列腺组织中PCNA抗原和Caspase-3蛋白的表达。结果 四黄前列片可缩小前列腺体积，降低腺腔的面积和腺上皮高度，并能抑制前列腺组织中PCNA的表达，增加Caspase-3的表达。结论 四黄前列片能抑制模型小鼠前列腺增生，其机理可能与抑制前列腺细胞的增殖和诱导凋亡有关。     

Effects of a new steroidal antiandrogen,TZP-4238 (17 α-acetoxy-6-chloro-2-oxa-4, 6-pregnadiene-3, 20-dione), on spontaneously developed canine benign prostatic hyperplasia

The effects of the new steroidal antiandrogen, TZP-4238 on spontaneouslydeveloped canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used for the treatment of BPH and prostatic cancer in Japan. Aged beagle dogs (5–9 years old) with spontaneously developed BPH (mean prostate volume, 17.7ml) were treated orally with a placebo, TZP-4238 (0.1 mg/kg/day, 0.01 mg/kg/day), or CMA (3 mg/kg/day), for 25 weeks. Prostate volume was measured by transrectal ultrasonography before treatment and every 5 weeks during treatment. TZP-4238 produced a regression in spontaneously developed canine BPH, its effects being more potent than those of CMA. TZP-4238 reduced the content of testosterone, dihydrotestosterone (DHT) and androgen receptor in the prostates of these animals, suggesting antiandrogenic mechanisms of the agent. TZP-4238 also appeared to reduce 5α-reductase activity by prevention of the androgen action in prostate as described above. © 1995 Wiley-Liss, Inc.     

Selective inhibition of androstenedione-induced prostate growth in intact beagle dogs by a combined treatment with the antiandrogen cyproterone acetate and the aromatase inhibitor 1-methyl-androsta-1,4-diene-3,17-dione (1-methyl-ADD)

Interference with estrogenic and androgenic actions might result in an inhibitory effect of benign prostatic hyperplasia (BPH). In the present study the effects of the treatment of intact, adult beagle dogs with the antiandrogen cyproterone acetate (CPA) and the aromatase inhibitor 1-methyl-ADD either alone or in combination on androstenedione-induced prostate growth and on testes, epididymides, and the pituitary was investigated. 1-Methyl-ADD induced a marked counterregulatory increase in the serum testosterone and dihydrotestosterone (DHT) concentrations leading to hyperplasia of the glandular part of the prostate. However, the aromatase inhibitor antagonized the androstenedione-induced (estrogen-related) stimulation of the fibromuscular stroma of the prostate. CPA caused a complete atrophy of the prostate that was also present after treatment with both the aromatase inhibitor and CPA in spite of a striking elevation of the serum testosterone and DHT levels and in spite of the antagonization of the inhibition of testes and epididymal weight induced by androstenedione plus CPA. This indicates a selective inhibition of the prostate of intact beagle dogs treated with CPA and 1-methyl-ADD.     

Role of canine basal cells in prostatic post natal development, induction of hyperplasia, sex hormone-stimulated growth; and the ductal origin of carcinoma

BACKGROUND: The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men it appears to be rare in dogs and unlike the disease in humans it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells. METHODS: Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from 19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5 alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5 alpha-androstane-3 alpha diol and estradiol-17 alpha as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), Pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67. RESULTS: We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI-67. In contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The numbers of HMC and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR which suggests that androgens may not be required for the initiation or progression of these cancers. CONCLUSIONS: Our findings indicate that two biologically distinct populations of basal cells may exist in the canine prostate. In this regard the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development. Prostate 47:149-163, 2001.     

Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma

BACKGROUND: The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells. METHODS: Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5alpha-androstane-3alpha diol and estradiol-17alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67. RESULTS: We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI-67. In contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The numbers of HMC and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR, which suggests that androgens may not be required for the initiation or progression of these cancers. CONCLUSIONS: Our findings indicate that two biologically distinct populations of basal cells may exist in the canine prostate. In this regard, the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally, we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together, these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development.     

Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia.

The effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One- to 2-year-old beagle dogs were castrated and administered 75 mg/week of androstanediol (A-diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP-4238, 0.1 mg/kg/day of TZP-4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A-diol plus E2. Treatment with 0.5 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP-4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/kg/day of TZP-4238 decreased 5 alpha-reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP-4238 and CMA were effective in inhibiting the growth of hormone-induced canine BPH, and TZP-4238 was at least 5 times more potent than CMA. TZP-4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen-AR complex. TZP-4238 decreased 5 alpha-reductase activity by prevention of the androgen action described above.     

Fast Facts: Prostate Cancer

OBJECTIVE

To characterize the changes in androgen levels in the prostate after castration, as androgens are critical in the progression of prostate cancer after castration, but the time at which the androgen remaining in the prostatic cancer tissue after castration exerts its effects is poorly understood.

MATERIALS AND METHODS

The ventral prostate (VP) in adult male spontaneously hypertensive rats was excised at 2, 4 and 8 h, 1, 2, 4 and 7 days, and 2, 4 and 8 weeks after castration. The dihydrotestosterone (DHT), testosterone, dehydroepiandrosterone (DHEA) and androstenedione (4‐dione) levels in the VP were measured simultaneously using gas chromatography/tandem mass spectrometry.

RESULTS

Within 2 days of castration, the DHT and testosterone levels in the VP decreased sharply, while there were no significant changes in the DHEA or 4‐dione levels. From 2 days to 2 weeks after castration (2–7 days for 4‐dione), there was a sharp peak in tissue androgen levels in the VP (P < 0.05 for all androgens); during the subsequent 6 weeks after castration, all of the tissue DHT, testosterone, DHEA and 4‐dione levels gradually increased with time.

CONCLUSIONS

These data show the changes which occur in androgen levels in rat VP after castration and support the concept that the adrenal glands compensate for the loss of testicular androgen.     

In vivo studies on the antiandrogenic effects of cimetidine versus cyproterone acetate in rats

To investigate the antiandrogenic action of cimetidine in vivo, prostatic androgen uptake and metabolism, spermatogenesis, morphology of the prostate and testes, and plasma hormone levels were studied using Sprague-Dawley rats, and the results were compared with the effects of cyproterone acetate or castration. Cimetidine and cyproterone acetate caused significant reduction in the weights of the ventral prostate and testes. The changes of ventral prostate were accompanied by a dose-related epithelial atrophy. No adverse effect on spermatogenesis was observed after treatment with cimetidine at daily doses of 50 mg/kg or cyproterone acetate of 10 mg/kg. Although cimetidine treatment induced a significant decrease in plasma testosterone levels, the uptake of testosterone-3H and its conversion to DHT of the ventral prostate were not inhibited by cimetidine.     

Effect of age, castration, and testosterone replacement on the development and restoration of canine benign prostatic hyperplasia

An experiment was designed to test the effect of castration and testosterone replacement on the development of benign prostatic hyperplasia (BPH) in young and on the restoration of BPH in old beagles. Twenty beagles were divided by age into young (1.5-2.5-yr) and old (6.0-8.5-yr) groups. Each of these groups was further divided randomly into two additional groups of age-matched, intact, untreated control and castrate beagles. The latter were then treated with testosterone-filled Silastic implants designed to clamp serum testosterone at concentrations similar to those observed in adult beagles for 7 months beginning 5 months after castration. Histopathologic characterization of each prostate was completed on biopsy material obtained at the beginning and end of the experiment. Prostate weights were determined each month for 12 months via a noninvasive two-dimensional X-ray procedure. Testosterone treatment for 7 months allowed BPH to develop in young and restored BPH in old beagles. These results suggest that testosterone in the adult beagle acts permissively to allow BPH to develop in the prostate of the aging dog. Some other testicular product may be required for the continued growth of BPH in aged beagles.     

Prevention and treatment of experimental prostate cancer in Lobund-Wistar rats. I. Effects of estradiol, dihydrotestosterone, and castration

The Lobund-Wistar (L-W) rat is unique in its susceptibility to spontaneous and induced metastasizing prostate adenocarcinomas (PAs). A single IV inoculation of methylnitrosourea (MNU) produced PAs in 20% of L-W rats in 12 months. The combination of MNU plus two to seven slow-release implants of testosterone propionate (TP) induced PAs in 50-90% of rats respectively in an average of 11.5 months. The induction of PAs was prevented by early treatments of rats at risk with estradiol and less so with dihydrotestosterone (DHT). However, on a technical basis, the results were not significant. Treatments of MNU-inoculated rats with estradiol, with DHT, or by castration, at intermediate points in the projected latency time of tumor development, reduced significantly the incidences of PA development. Rats in which overt PAs had already developed in response to 12 months of exposure to implants of TP did not respond to treatment by estradiol, DHT, or castration. Thus there are early stage(s) in induced prostate tumorigenesis in L-W rats that are sensitive to modulating agents.     

Transrectal ultrasonometry of the prostate: the prognostic relevance of volume changes under endocrine management

Summary Since 1980, a total of 55 patients with previously untreated prostatic carcinoma have been managed by castration and were followed regularly by means of transrectal ultrasonometry of the prostate. During the period of the study, distant metastases occurred in 20 patients; 10 showed progression after less than 1 year and 10 after more than 1 year. All patients showed a decrease of prostatic volume following castration. In the group of 10 patients who progressed within 1 year after castration, the initial volume reduction of the prostate was significantly smaller than in the rest of the patients. In patients whose prostatic volume decreased to at least 50% of the pretreatment volume after 3 months, none developed distant progression within 1 year. Of those patients whose prostatic volume did not decrease to at least 70% of the pretreatment volume after 3 months, 78% developed distant progression before or after 1 year. There was no significant difference in the volume decrease observed in patients who showed progression later than 1 year after initiation of treatment as compared to those patients who did not show progression at all. This prognostic information was compared to the impact of other commonly used prognostic factors, such as T-category, N- and M-status and grading. None of these factors reproduced the predictive value of the volume changes of the primary tumor. It therefore seems that transrectal ultrasonometry of the primary tumor has a place in monitoring the effects of endocrine management. The prediction of progression in 78% of the patients with prostatic volume >70% may be of limited clinical value now, but will be of greater importance as soon as effective treatment for hormone-unresponsive prostatic carcinoma becomes available.     

Influence of hormone treatment on prostate growth and micturition characteristics of the rat

The influence of dihydrotestosterone propionate (DHT) and estradiol (E) on prostate growth and micturition was evaluated. Complete studies were carried out on 49 Sprague-Dawley rats over a 14-day period. Rats were divided into three groups: (1) controls, (2) DHT, and (3) DHT + E. All groups were injected daily with 0.1 ml of sesame oil, together with 1.25 mg/kg of DHT for group 2 and 1.25 DHT + 0.125 mg/kg E for group 3. Physiological measurements of micturition were done weekly by subcutaneously administering a fluid loading dose consisting of 10 mg/kg furosemide + 5 ml saline. Parameters of micturition frequency, volume, and prostate weight were calculated. Prostate weight values for controls were 0.89 ± 0.06 g while those treated with DHT increased significantly to 1.26 ± 0.10 g (P < 0.05) and those treated with DHT + E also increased significantly to 1.24 ± 0.09 g (P < 0.05). There was no significant difference in prostate weight between the DHT and DHT + E groups. Analysis of micturition data shows that the mean volume voided per micturition decreases in both the DHT and DHT + E treated rats. At between 7 and 14 days of DHT and DHT + E treatment, rats micturated at significantly reduced mean volumes. The lowest mean volume per micturition was detected on the 14th day of DHT treatment, showing a significant reduction from control values of 3.05 ± 0.27 to 1.68 ± 0.05 ml. The corresponding value of the mean micturated volume in the DHT + E groups was 1.86 ± 0.31 ml. Control values for frequency of micturition was 3.25 ± 0.52/hr, while for rats treated with DHT it was 3.62 ± 0.38/hr and for DHT + E it was 4.0 ± 0.54/hr. Evidence is provided to demonstrate that 14 day DHT, and particularly DHT + E, stimulation produces significant alterations in prostate weight and micturition characteristics of unanesthetized rats. On the basis of these observations it is proposed that the hormonally enlarged prostate promotes stimuli to trigger the spinal micturition reflex, thereby producing increased frequency of micturition. © 1996 Wiley-Liss, Inc.     

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.     

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.     

Involution of spontaneous benign prostatic hyperplasia in the dog under the influence of chronic treatment with a LHRH agonist

Eight dogs with spontaneous benign prostatic hyperplasia were treated with daily subcutaneous injections of 25 micrograms of Buserelin, (D-Ser(TBU)6,des-Gly-NH2(10))ethylamide during 3 months. Prostate weight before treatment was estimated by tridimensional measurements during open surgery. After 3 months of treatment, prostate weight was decreased by 50-60% In two castrated control animals, prostate weight decreased about 70% after 3 months. Histological pattern in prostates from castrated or Buserelin-treated animals was similar and indicated considerable atrophy of glandular epithelium and predominance of stroma. At the same time, testes weight decreased with complete disappearance of spermatogenic activity. Acid phosphatase and arginine esterase activity levels, two markers of androgenic action in the prostate, were similar after Buserelin or castration. Steroid receptors for androgens, estrogens, and progesterone also behaved similarly under the influence of Buserelin and castration.