Changes in testosterone and dihydrotestosterone levels in male rat accessory sex organs, serum, and seminal fluid after castration: establishment of a new highly sensitive simultaneous androgen measurement method

It is known that abnormal androgen dynamics in the tissues is a cause of androgen-dependent disorders. Investigation of tissue androgen levels could provide a clue to the elucidation of disorders. However, it is difficult to measure a trace amount of androgen in the tissues. We established a highly sensitive simultaneous quantification method of testosterone and dihydrotestosterone (DHT), which play the most important roles in the body among androgenic steroids in trace amounts, and investigated time course changes in testosterone and DHT levels in male accessory sex organs, serum, and seminal fluid after castration in rat models. In addition, changes in the testosterone/DHT ratio of male accessory sex organs and seminal fluid were observed. The simultaneous testosterone and DHT measurement method established by us was validated. Intra-assay variation and interassay precision and accuracy were all within +/-20%, and the quantification limits of testosterone and DHT were both 15.6 pg/g. With the use of this method, the testosterone and DHT levels in the prostate, seminal vesicles, and serum immediately after castration were similar to those previously reported. The testosterone and DHT levels were 350 pg/g and 605 pg/g, respectively; which showed dominance of DHT in seminal fluid, although it was not as marked as that in the male accessory sex organs. Androgens decreased with time after castration in the accessory sex organs, serum, and seminal fluid. In the prostate and seminal vesicles, testosterone and DHT decreased to about 50% and about 2% of the normal levels, respectively, 72 hours after castration. The serum levels were under the quantification limits 6 hours after castration and thereafter. In seminal fluid, the testosterone and DHT levels decreased to 49% and 35% of normal levels, respectively, 72 hours after castration. The testosterone/DHT ratio in the male accessory sex organs was lower in the prostate (0.06) than in the seminal vesicles (0.13) immediately after castration. In the seminal fluid, changes in the ratio were small compared with those in the accessory sex organs and serum. These results showed that our method was capable of measuring testosterone and DHT in very small amounts of samples such as prostate biopsy specimens, and it might provide a clue to the elucidation of the pathology of androgen-dependent disorders.     

Influence of age, strain, and the testes on rat prostate hormone sensitivity

There are conflicting reports in the literature regarding the response of the rat prostate to various androgen/estrogen combinations. The reason for these conflicting results has been unclear. The purpose of the present study was to assess factors that may determine the effect of sex hormones on rat prostate growth. The results of this study demonstrate that the prostates of Lewis rats respond differently to sex hormone combinations than do those of Sprague Dawley rats. Young rats have a different prostate hormone responsiveness than do old rats. The presence or absence of the testes alters the responsiveness of the prostate gland to androgen-estrogen combinations. These results suggest that strain, age, and the presence of the testes are important factors which will influence the response of the rat prostate to hormonal manipulation. The importance of these factors should be considered in the design of experiments which deal with the response of the rat prostate to hormone manipulation.     

The effects of ketoconazole on testosterone production and normal and malignant androgen dependent tissues of the adult rat

Ketoconazole is a potent inhibitor of the P450 series of enzymes that are essential for the production of androgens. In order to determine the effects of ketoconazole on androgen production and androgen dependent tissues in the rat, adult male rats were administered varying doses of ketoconazole every 12 hours. Serum testosterone declined to unmeasurable levels at ketoconazole doses of greater than 4 mg. This dose was sufficient to completely inhibit the testosterone surge induced by the administration of a potent luteinizing releasing hormone agonist. The ventral prostate weight of normal rats and the volume of the Dunning R3327H androgen dependent prostatic cancer declined at the same rate in animals treated with ketoconazole or castration. Ketoconazole may be an effective agent to treat androgen dependent diseases.     

Clusterin is not essential for androgen-regulated involution and regeneration of the normal mouse prostate

BACKGROUND: Inhibition of clusterin expression has been shown to enhance the sensitivity of prostate cancer cells to chemo and hormone therapy. Clusterin antisense oligonucleotides (ASOs) are currently in phase II human clinical trials for treatment of hormone refractory prostate cancer. However, the role of clusterin in androgen-regulated involution and regeneration of the normal prostate gland has not been established. METHODS: Prostate involution and regeneration was examined in clusterin-deficient mice undergoing up to three cycles of androgen withdrawal and restoration. RESULTS: Surprisingly, clusterin deficiency did not affect the apoptotic index, and the temporal biochemical and morphological changes associated with involution and regeneration of the normal adult prostate following multiple rounds of androgen withdrawal and replacement. CONCLUSION: Clusterin is not critical for normal prostate development or androgen-regulated involution and regrowth of the mouse prostate gland, suggesting that clusterin may have distinct functions in malignant versus normal prostatic epithelial cells.     

Development of androgen resistance in mouse mammary tumor cells can be prevented by the antiandrogen flutamide

As has been clearly demonstrated in prostate and breast cancer, progression to hormone insensitivity is a major problem responsible for the usually partial and short-lived response to antihormonal therapy. Preincubation of androgen-sensitive Shionogi mouse carcinoma cells for 15 days in the absence of androgens causes the development of complete resistance of cell growth to androgens. Of potentially important therapeutic significance is the finding that androgen sensitivity can be maintained not only by the androgen dihydrotestosterone (DHT) but also by incubation with the pure antiandrogen Flutamide-OH in the absence of androgens. Since androgen resistance is one of the main problems facing the treatment of prostate cancer, the possibility of avoiding or at least delaying the development of androgen resistance with a pure antiandrogen could well provide the basis for improving the success of therapy for this disease.     

Downregulation of androgen, estrogen and progesterone receptor genes and protein is involved in aging-related erectile dysfunction

We hypothesize that downregulation of sex hormone receptors (androgen, estrogen and progesterone receptors) is involved in aging-related erectile dysfunction. To test this hypothesis, we investigated the expression of sex hormone receptors in penile crura of aging rats. A total of 40 rats were divided into four groups based on age (6, 12, 18 and 24 months), and the erectile function was analyzed by the measurement of intracavernous pressure. Gene and protein expressions of sex hormone receptors were analyzed by RT-PCR and immunostaining, respectively. The mean intracavernous pressures of 6-, 12-, 18- and 24-month-old rats were 110.1, 89.6, 73.5 and 42.7 cm H(2)O, respectively. Gene and protein expressions for androgen receptor, estrogen receptor-beta and progesterone receptor were present in similar levels in 6-, 12- and 18-month-old rat crura, but significantly lower or absent in 24-month-old crura. This is the first study to demonstrate that downregulation of sex hormone receptors in aging rat crura is associated with erectile dysfunction.     

Autoradiographic localization of estrogen and androgen target cells in human and rat prostate carcinoma

The distribution of estrogen target cells within the Dunning R3327-H rat prostate tumor following intravenous injection of tritiated estradiol into rat hosts was compared to the distribution obtained following incubation of a 2 mm. sample of the tumor with tritiated estradiol in organ culture. No difference was observed, indicating that the in vitro method was an effective approach for autoradiographic analysis of tumor biopsy samples. Subsequently, tumor samples were excised from solid tumors of R3327-H and R3327-MAT LyLu tumors growing in Copenhagen rats. These tumor models were chosen as representatives of hormone sensitive (R3327-H) and hormone insensitive (R3327-MAT LyLu) tumors. Normal rat dorsal prostate and human tumor biopsy samples were also studied. Autoradiographic studies were performed in vitro utilizing tritiated estradiol and tritiated dihydrotestosterone to compare the distribution of estrogen and androgen target cells. The present research demonstrated that 1) similar patterns of nuclear uptake of steroids are obtained with in vivo and in vitro autoradiographic techniques, 2) estradiol receptors occur primarily in extra-acinar epitheloid cells in both rat and human prostate carcinomas, 3) these epithelioid cells are not characteristic of the normal rat dorsal prostate, 4) androgen receptors occur in both acinar and stromal epithelioid cells in rat and primarily in acinar epithelial cells in human tumors and 5) in vitro autoradiographic methods can provide insight into differences in sensitivity to steroids which may be of diagnostic importance in the treatment of cancer.     

Characterization of steroid receptors in human prostate using mibolerone

Accurate quantitation of androgen receptors requires a radioactive ligand which has affinity and specificity for the receptor and which is stable to metabolic enzymes. In this report, we have characterized the properties of 7 alpha,17 alpha-dimethyl-17 beta-hydroxy-4-estren-3-one (mibolerone) in human benign hyperplastic prostate cytosol and compared them to those of 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one (R1881). Mibolerone was found to have an affinity (Kd = 1.5 nM) greater than R1881. (Kd = 2.3 nM) for the androgen receptor in human prostate tissue. Surprisingly, mibolerone was found to bind with high affinity to the progesterone receptor in both human prostate (Kd = 5.9 nM) and rabbit uterus (Kd = 1.1 nM). However, binding to this receptor in both species could be blocked with a 500-fold excess of triamcinolone acetonide. [3H]Mibolerone binding to the androgen receptor was competed effectively with unlabeled dihydrotestosterone, R1881, and mibolerone but not by progesterone, diethylstilbestrol or R5020, in the presence of triamcinolone acetonide. Interestingly, mibolerone was more resistant to metabolism than R1881 in prostate cytosol when exposed to elevated temperatures (30 degrees C) for extended periods of time. However, when exposed to high-intensity ultraviolet irradiation, both compounds lost 50% of their binding ability in about 30 minutes. Mibolerone was found to have a very low affinity (Ki = 540 nM) for human sex steroid binding protein. These studies demonstrate that mibolerone is a useful ligand for androgen receptor assays. They also emphasize the need for including competitors of progesterone receptor binding in assays utilizing this steroid for androgen receptor measurements.     

Androgen regulation of spermidine synthase expression in the rat prostate

BACKGROUND: Spermidine synthase, an essential enzyme in the polyamine synthesis pathway, was identified as one of the androgen-response genes in the rat ventral prostate. Characterization of androgen regulation of spermidine synthase is important to the understanding of androgenic regulation of polyamine synthesis. METHODS: Full-length cDNA encoding rat spermidine synthase was isolated from a lambdaZAP cDNA phage library. Young male adult Sprague-Dawley rats were used for castration and androgen replacement. Northern blot and in situ hybridization were used to characterize gene expression. RESULTS: The amino acid sequence of rat spermidine synthase shares 99% and 94% identity with that of mouse and human spermidine synthase, respectively. Spermidine synthase gene is abundantly expressed and regulated by androgens in the ventral, dorsal, and lateral lobes of the rat prostate, and its expression is localized to the epithelial cells. Spermidine synthase also is regulated by androgens in the seminal vesicles but not in the muscle, brain, kidney, thymus, heart, or liver, suggesting that this enzyme is responsive to androgen in the male sex accessory organs only. The expression of spermidine synthase and two other enzymes involved in polyamine synthesis, S-adenosylmethionine decarboxylase and ornithine decarboxylase, are regulated by androgens coordinately. CONCLUSIONS: Spermidine synthase is most abundantly expressed and regulated by androgens in the prostatic epithelial cells, suggesting that regulation of spermidine synthase is likely a key step in coordinated androgen regulation of polyamine synthesis in the prostate.     

LY207320 (6-methylene-4-pregnene-3,20-dione) inhibits testosterone biosynthesis,androgen uptake, 5α-reductase,and produces prostatic regression in male rats

LY207320 is an in vitro inhibitor (estimated IC₅₀ = 0.06 μM) of steroid 5α-reductase that catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT). In contrast, LY207320 was only moderately active against rat prostatic 5α-reductase in vivo (32% inhibition at 50.0 mg/kg single dose). LY207320 did, however, inhibit the in vivo uptake of [³H]-T by the prostate. The antiprostatic and endocrine effects of this agent were evaluated following daily (21 days) administration to castrated, androgen-supplemented castrate, and intact rats. LY207320, which has modest progestational competitive binding activity, does not bind to rat prostatic androgen or uterine estrogen cytosolic receptors. In the castrated male rat, subcutaneously (s.c.) administered LY207320 had no androgen agonist activity, as evidenced by a lack of accessory sex organ weight gains. Administration of s.c. LY207320 to intact rats for 21 days at doses greater than 5.0 mg/kg-day produced significant (P <0.05) reductions of seminal vesicle and ventral prostatic weights (maximal regression = ?65% and ?40% from control values, respectively at 50.0 mg/kg-day). The compound had no regressive activity on male accessory sex organs when administered orally. LY207320 did not alter circulating prolactin, LH, or corticosterone levels, but at high doses (>m50.0 mg/kg-day), lowered circulating T[?67% from intact control levels (P <0.05)]. Histological analysis of the rat ventral prostates (RVPs) in LY207320-treated rats was consistent with an androgen-deprived state. Decreased circulating androgens and prostatic regression are associated with inhibition of testicular 17α-hydroxy/C17,20-lyase enzyme activity (IC⁵⁰ = 0.06 μM). These findings support the contention that LY207320 is a physiological antagonist of androgen action in male rats, and that its effects are mediated primarily through inhibition of testicular androgen production rather than accessory sex organ 5α-reductase. © 1993 Wilcy-Liss, Inc.     

Testosteron und Prostata

The normal development and function of the prostate, as well as its pathological growth, are governed by a lifelong dependency on endogenous androgens, the majority of which are of testicular origin. In contrast to other androgen-sensitive tissues, androgenic effects in the prostate are only exerted by the intracellular metabolite dihydrotestosterone. Conflicting evidence exists regarding changes of the intracellular prostatic androgen receptors in benign prostatic hyperplasia and prostatic carcinoma. Equally conflicting is the clinical evidence concerning androgen metabolism in patients with manifest or metastatic prostate cancer. So far, there is no clear evidence for an increased risk of prostatic neoplasia with testosterone substitution in absolute or partial androgen deficiency. However, in view of the high prevalence of latent prostate cancer, caution is advisable.     

Correlated biochemical and stereological studies on testosterone metabolism in the stromal and epithelial compartment of human benign prostatic hyperplasia

The growth and function of the human prostate is dependent upon a continuous supply of androgens, mainly 5 alpha-dihydrotestosterone, the 5 alpha-reduced metabolite of testosterone. Within the human prostate dihydrotestosterone is thought to be the intracellular mediator of androgen action. Although it is well documented that dihydrotestosterone is evenly distributed between the stromal and epithelial compartment of the prostate, the anatomical localization of dihydrotestosterone formation within the normal and hyperplastic prostate is still not established. To provide further insight into this problem we have measured, under conditions approximating the in vivo state, dihydrotestosterone formation in prostates obtained from 4 men with normal prostates and 36 men with benign prostatic hyperplasia. In addition to this we have performed histometric analysis of the cellular composition of the samples incubated, in order to correlate the morphological and the histochemical findings. Dihydrotestosterone is the major metabolite, and androstanediol and androstenedione were formed in smaller quantities. Under the given conditions metabolite formation from testosterone increased linearly for 60 minutes and the half maximum rate of dihydrotestosterone formation (Km) was observed at about 1.25 X 10(-6) M testosterone, a value similar to that reported for rat prostatic nuclei and human prostatic tissue. Dihydrotestosterone formation was higher in hyperplastic prostates than in the normal prostate. (Student's t test: p less than 0.05). The stroma in both the normal and hyperplastic tissue converts testosterone to dihydrotestosterone very actively. No significant relation was found between dihydrotestosterone formation and the per cent distribution of the stromal and epithelial compartment in any sample studied. In conclusion, our results are compatible first with the thesis that the rate of dihydrotestosterone formation is increased in the hyperplastic prostate and secondly with the concept that the rate of dihydrotestosterone formation is approximately the same in the epithelial and stromal compartments of the prostate.     

Action of prolactin in regressing prostate: Independent of action mediated by androgen receptors

Hyperprolactinemia, achieved by grafting pituitaries under the renal capsule, has been shown to cause a delay in the rate of castration-induced prostatic regression in rats. The mechanism of this prolactin action is not established, although it has been suggested that the action of prolactin in the rat prostate is mediated through the action of androgen. To explore the possibility that a small amount of residual endogenous androgen present in the prostate at the time of castration acts synergistically with prolactin to cause this delay in prostatic regression, Flutamide has been used in the present study in an attempt to inhibit this residual androgen effect by blocking its interaction with androgen receptors. Two experiments were conducted. In experiment 1, daily sc injections of Flutamide (25 mg/kg) for 7 days to castrated rats supplemented with dihydrotestosterone-filled silastic tubing either 1 or 4 cm long completely suppressed both prostatic weight and protein content to the level that was normally observed in castrated rats receiving empty tubings. Furthermore, treatment of Flutamide to castrated rats did not cause an increase in prostatic weight and protein content over those of castrated rats treated with the vehicle only. These results indicate that Flutamide, at this dosage, is a potent antiandrogen and that the compound itself does not have any androgenic activity in the rat prostate. In experiment 2, adult male rats were castrated and received two female pituitaries grafted under the renal capsule. One week later, their serum prolactin levels increased from 20±3 ng/ml to 102±8 ng ml. This elevated level of serum prolactin was associated with a delay in the rate of prostatic regression. Administration of Flutamide, at a dose (25 mg/kg) which completely suppressed prostatic growth, failed to inhibit the delay in prostatic regression in castrated rats bearing the pituitary grafts. Since Flutamide inhibits the androgen action in the prostate by blocking the binding of intracellular dihydrotestosterone to androgen receptors, the failure of Flutamide to block the effect of prolactin suggests that the prolactin action in regressing prostates is not mediated by androgen receptors.     

Hormonal control of accessory sex organ fibromuscular stroma

Using the surgically separated epithelium and muscle preparation of the guinea pig seminal vesicle, quantitative determinations were made of the hormonal sensitivities of three components of male accessory sex organ fibromuscular stroma. The parameters measured were epithelial collagen, muscle tissue cell number, and muscle tissue collagen. Epithelial collagen increased approximately tenfold between one week of age and adulthood. This growth was completely prevented by castration and was sustained at normal levels of maintenance of prepubertal castrates with dihydrotestosterone (DHT). Castration of adult animals reduced epithelial collagen 40%; such reductions were prevented by DHT treatment. Estrogen treatment of adult castrates, either alone or in combination with DHT, had no anabolic effect on the epithelium. In all of these studies, changes in epithelial collagen correlated with changes in epithelial wet weight, DNA content, and RNA/DNA. From 1 week of age to adulthood, growth of seminal vesicle muscle involved marked increases in wet weight, DNA content, RNA/DNA, and collagen content. Increments in all parameters were prevented by prepubertal castration and were sustained at normal levels in castrates by DHT treatment. However, in adult animals, muscle DNA content and collagen levels were insensitive to castration and androgen replacement; only tissue weight and cell size (RNA/DNA) were androgen sensitive. Estrogen treatment of adult castrates caused supranormal increases in muscle DNA and collagen; changes in collagen were irreversible. The effects of simultaneous treatment of DHT and estrogen did not differ from those of DHT alone. Therefore, normal postnatal development of the stromal components, epithelial collagen, muscle cells, and muscle collagen was androgen dependent, but in adult animals, only epithelial collagen retained androgenic sensitivity. Estrogen induced supranormal and irreversible growths in the muscle.     

Androgen receptors in osteoblast-like cell lines

Summary Although androgens exert major effects on bone remodeling, the mechanisms by which they exert their effects remain unclear. Recently, it has become apparent that receptors for sex steroids may be present in osteoblastic cells. We have examined several cell lines with osteoblastic phenotypes to determine if specific, high affinity androgen receptors are present. Two cell lines of human origin (Saos-2 and U2-OS) and one of rat origin (UMR-106.01) were studied. Androgen binding sites were present in all cell lines. Binding affinities were high (K_D=1.6−2.5×10⁻¹⁰ M), and similar to those in classical androgen target tissues (prostate, kidney). Concentrations were greater in the human cell lines (1277 and 1605 sites/cell) than in the rodent line (74 sites/cell). In the human cell lines androgen binding was also specific and typical of androgen receptors in other tissues. Specific estrogen binding was not present in the UMR-106.01 cells, and no estrogen receptors were detectable in the human cell lines using an enzyme-linked receptor immunoassay. Specific binding for progesterone was also absent in the UMR-106.01 cells, but progesterone receptors were detected immunologically in the Saos-2 (119 sites/cell) and U2-OS (118 sites/cell) lines. These findings indicate the presence of androgen receptors that are of similar character to those in classical androgen target tissues, and suggest that the study of these cell lines may be useful in the study of the regulation of androgen effects in osteoblasts.     

Effect of long‐term testosterone propionate or human chorionic gonadotrophin administration on reproductive glands in adult male rabbits

The study was aimed to investigate the effect of testosterone propionate (TP) or human chorionic gonadotrophin (hCG) treatment on reproductive glands in sexually mature male rabbits. A total 36 adult male rabbits were randomly distributed to six equal groups. The first control group (CON), the second treated with low‐dose TP (TPL), the third treated with high‐dose TP (TPH), the fourth treated with low‐dose hCG (CGL), the fifth treated with medium‐dose hCG (CGM) and sixth treated with high‐dose hCG (CGH). At the 16th post‐treatment week, the animals were sacrificed, and the testes and accessory sex glands dissected, weighted and stored at ?20 °C until assay. Testosterone propionate treatment in both doses resulted in reduction (P < 0.01) in testicular weight and increase (P < 0.01) in weight of vesicular gland, paraprostate and proprostate glands. High‐dose TP increased the weight of prostate and bulbouretheral gland (BUG). Testosterone propionate increased total androgen (P < 0.01) with Testosterone (T) predominating in serum, dihydrotestosterone (DHT) predominating in testes and most accessory sex glands. High dose of hCG increased the weight of proprostate and paraprostate glands. Androgen level in serum, testes and accessory sex glands increased (P < 0.01) after hCG treatment.     

Hormonal prevention of prostate cancer

Prostate cancer is disease in which the mortality rate is highly variable among populations. An increasing risk with migratory changes suggests that some environmental factor or factors influence prostate cancer risk. It is well established that the prostate is hormonally influenced. Carcinogenesis is a process of malignant transformation evolving over time, involving cellular growth and division. There is evidence suggesting that androgenic influences over a period time encourages the process of prostate carcinogenesis. Studies of prostate biology support the concept that dihydrotestosterone is the principal androgen responsible for both normal and hyperplastic growth of the prostate gland. It may be that androgen causes prostate carcinogenesis. Suppression of dihydrotestosterone synthesis may inhibit carcinogenic transformation. Some preclinical and clinical observations support this hypothesis. A placebo controlled randomized trial using finasteride, an inhibitor of 5-alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, is ongoing. The endpoint of this trial is reduction of prostate cancer incidence.     

Regulation of androgen and vitamin d receptors by 1,25-dihydroxyvitamin D3 in human prostate epithelial and stromal cells

PURPOSE: The mechanisms of the interaction between 1,25-dihydroxyvitamin D(3) (1,25 D) and androgens, and their respective receptors in their action on the prostate are not completely understood. We examined the interplay of 1,25 D and androgens on the epithelial and stromal cells of the prostate. MATERIALS AND METHODS: The human neonatal prostatic epithelial cell line 267B-1 (BRFF, Inc., Ijamsville, Maryland) and primary cultures of human prostate stromal cells were treated with medium containing 5 or 10 microM 1,25 D or ethanol (control) in the presence or absence of 10 nM dihydrotestosterone (DHT) (Sigma Chemical Co., St. Louis, Missouri). Protein levels of androgen receptor (AR) and vitamin D receptor (VDR) were determined by immunoblot analysis of whole cell extracts. Electrophoresis mobility shift assays were used to determine AR and VDR DNA binding activities. RESULTS: The VDR protein level of 267B-1 cells was increased in the presence of 1,25 D (with the maximum effects seen at 24 hours) regardless of the presence or absence of DHT. In addition, exogenous DHT increased the AR and VDR DNA binding activities of 267B-1 and stromal cells in the presence of 1,25 D. CONCLUSIONS: ARs in the normal prostate are regulated by androgens, whereas VDRs in the normal prostate can be regulated by 1,25 D as well as by other androgens such as testosterone. This finding further supports the concept that 1,25 D as a steroid hormone, in addition to other androgens such as DHT, may have a role in the growth and differentiation of normal prostate.     

细胞凋亡和性激素环境与前列腺增生的关系

目的探讨雄雌激素、细胞凋亡在前列腺增长和前列腺增生（ＢＰＨ）发病中的作用。方法应用ＤＮＡ末端原位标记的方法对正常前列腺移行带（１０例）和周围带（１０例）以及ＢＰＨ组织（２０例）标本进行了细胞凋亡率的研究,并应用放射免疫学技术检测了相应组织的双氢睾酮（ＤＨＴ）和雌二醇（Ｅ２）含量。结果正常前列腺移行带,周围带ＤＨＴ和Ｅ２的差异无显著性,ＢＰＨ组织中的Ｅ２含量（平均６．６３ｎｇ／ｇ蛋白）虽高于正常前列腺的移行带含量３．１５ｎｇ／ｇ蛋白,但差异无显著性（Ｐ＝０．１）。正常前列腺周围带细胞凋亡率（４１．２±３．９）％显著高于移行带（２９．７±４．０）％,Ｐ＜０．０５,后者又非常显著地高于ＢＰＨ组织（３９±１．１）％,Ｐ＜０．００１。正常与增生前列腺组织内的ＤＨＴ及Ｅ２含量与细胞凋亡率之间无明显相关性。正常前列腺组织中,前列腺增生的起始部位移行带的细胞凋亡率已明显下降,随着年龄的增长,凋亡率进一步下降,导致ＢＰＨ。细胞凋亡率与其组织的ＤＨＴ、Ｅ２无明显相关性。结论前列腺导管系统的远、近端（周围带、移行带）上皮细胞结构形态不同,其周围的间质亦有差异,因此即使在接受相同量的雄、雌激素情况下,这些细胞的反应并不相同。     

Non-androgenic role of testis in enhancing ventral prostate growth in rats

This study was conducted to investigate whether the testis, aside from its ability to secrete androgen, is able to promote prostatic growth in rats. Increasing quantities of silastic capsules filled with crystalline dihydrotestosterone (DHT) were implanted subcutaneously into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham operation on the testes. Control animals received empty capsules. Twenty-eight days later, the growth of the ventral prostate as measured by wet weight, DNA, and protein content per prostate was significantly greater in rats with intact testes than in orchiectomized rats. An overall increased growth was noted at all doses of exogenous DHT administered. Serum levels of luteinizing hormone in animals treated with DHT were undetectable. Serum levels of testosterone in intact rats treated with DHT were not significantly different from those in castrated rats. These observations suggest a non-androgenic role for the testis and, perhaps, epididymis in promoting prostatic growth in rats, and are consistent with the concept that a non-androgenic substance, produced from the testis and/or epididymis, is able to enhance prostate growth induced by androgen stimulation. The possibility that this phenomenon may play a role in the benign growth of the prostate observed in aging human males with decreased blood levels of androgen warrants consideration.