Freeze-fracture,ultrastructural and autoradiographic analysis of the ventral prostate glands in castrated mice

Summary Ultrastructure of the ventral prostate glands was studied in mice castrated for 1 through 60 days and for 11 and 17 months and in age-matched normals. We have described freeze-fracture and ultrastructural characteristics of acinar epithelial cells in addition to the patterns of thymidine incorporation in the cells of castrates and normal animals. Our study has shown a biphasic pattern of prostatic involution in the long-term castrated mice. In castrates the initial atrophy of prostate glands occurred by sloughing of the apical portions of columnar cells, autophagia of the cytoplasmic organelles as well as by occasional sloughing of the individual cells into the acinar lumen. Concurrent with the initial atrophy, the glands and stroma were infiltrated by neutrophils and lymphocytes. The cell loss by sloughing and leucocyte infiltration of glands became infrequent in 7- to 21-day castrates. However, the cell loss by sloughing increased secondarily in mice castrated for 21 to 37 days along with the increased leucocyte infiltration of the glands. The cell loss became minimal in castrates of 60 days and beyond. Our evidence suggests that the cell loss by sloughing was an active process in the involution of prostate glands which also showed differential sensitivity to castration stimuli in mice.This research was supported by Medical Research Service of Veterans Administration     

Morphometric analysis of the rat ventral prostate and seminal vesicles during prepubertal development: effects of neonatal treatment with estrogen

In a morphometric study on the ventral prostate and seminal vesicles in the rat, we investigated the changes in fibromuscular stroma, glandular epithelium, and glandular lumen. Animals were studied at 15, 30 and 45 days of age. The rapid prepubertal growth started earlier in the ventral prostate than in seminal vesicles. In addition, the effects of neonatal administration of estrogens on the different tissue compartments were studied, comparing rats that had been castrated and/or treated with estrogen at birth to intact animals at 15 days of age. Estrogens caused a decrease in the volume of the glandular epithelium and increased the volume of the fibromuscular stroma in both ventral prostate and seminal vesicles. Castration partially abolished the estrogen-induced growth of the stroma, which suggests that the growth is dependent on testicular factors. The difference in proportion of the fibromuscular stroma between the two glands is evidence that the size of the whole seminal vesicles has increased whereas the size of the ventral prostate has decreased.     

Oxidative stress signalling in the apoptosis of Jurkat T-lymphocytes

Within the first 24 h after castration of an adult male rat, the vascular system of the ventral prostate gland undergoes a degenerative process that drastically reduces blood flow to the tissue. Since the vascular degeneration precedes the loss of the prostatic epithelium (by apoptosis), we have proposed that the onset of epithelial cell apoptosis in this tissue is caused by an ischemic/hypoxic environment resulting from the loss of blood flow. In order to further evaluate the extent to which ischemia/hypoxia might be a factor in apoptosis of the prostate epithelium after castration, we analyzed for biomarkers of cellular hypoxia in rat ventral prostates during the first 3 days following castration. Ventral prostate tissues removed from hypoxyprobe-1-treated adult male rats (uncastrated controls; surgically castrated for 24, 48 or 72 h, or sham-castrated for equivalent times) were directly analyzed for evidence of hypoxia by in situ immunohistochemical evaluation of hypoxyprobe-1 adduct formation in the prostate cells. Protein extracts from these tissues were also tested for expression of the 120 kDa hypoxia-inducible factor-1-alpha (HIF-1-alpha) protein as well as for expression of mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) proteins using a Western blot assay. The tyrosine phosphorylation status of the latter signaling molecules was also evaluated by Western blotting using anti-tyrosine phosphate antibodies. Our results showed that epithelial cells of the rat ventral prostate stained positively for hypoxyprobe-1 adducts at all times after castration, whereas cells in control tissues were unstained by this procedure. In addition, the prostatic expression of HIF-1-alpha protein was increased approximately 20-fold at 48 h after castration compared to control tissues. Finally, although prostatic MAPK and JNK protein expression was unaltered during the early period after castration, phosphorylation of the JUN kinase protein was significantly elevated, indicating that this stress-activated cellular signaling pathway becomes more active subsequent to castration. These results support our proposal that early castration-induced degeneration and constriction of the vascular system of the rat ventral prostate gland leads to reduced oxygenation of prostatic epithelial cells and the activation of hypoxic cellular signaling in these cells through upregulation of HIF-1-alpha expression and stimulation of the JUN kinase signaling pathway.     

Transforming growth factor beta 1 and androgen receptors in prostate neoplasia

OBJECTIVE: To investigate the interplay between transforming growth factor (TGF) beta 1, androgen receptors and stromal-epithelial interactions in benign prostatic hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and prostate carcinoma areas of prostate neoplasia. STUDY DESIGN: In this immunohistochemical study we investigated staining patterns and then determined the correlation between TGF-beta 1 expression and androgen receptor status in the epithelium and stroma of 60 paraffin-embedded tissues from radical prostatectomies. RESULTS: Staining patterns differed in the epithelium and stroma of tumor and peritumor prostatic tissue. TGF-beta 1 immunostaining (H-scores) in the epithelium and stroma increased significantly from BPH to PIN and from BPH to prostate carcinoma in the epithelium (P < .05), whereas androgen receptor (AR) immunoreactivity significantly (P < .05) increased from BPH to PIN to prostatic carcinoma in epithelium and stroma. TGF-beta 1 did not correlate with histologic grade of differentiation, whereas AR proteins were more strongly expressed in Gleason score 5 and 6 than score 7 tumors (P < .05). Nonlinear regression showed a significant correlation (P < .01) between TGF-beta 1 and AR expression only in the stromal compartment of PIN. CONCLUSION: These findings argue in favor of an interaction between TGF-beta 1 and AR in the early stages of prostate carcinogenesis and suggest that TGF-beta 1 plays a central role in stromal-epithelial interactions during the early stages of malignant transformation.     

Relations of Bromine,Iron, Rubidium,Strontium, and Zinc Content to Morphometric Parameters in Pediatric and Nonhyperplastic Young Adult Prostate Glands

The variation with age of the Br, Fe, Rb, Sr, and Zn mass fractions and some histological characteristics of intact prostate glands of 50 subjects aged 0–30 years was investigated by an energy-dispersive X-ray fluorescence and a quantitative morphometric analysis. Mean values?±?standard error of the mean (M?±?SΕΜ) for the mass fractions (in milligrams per kilogram wet-mass basis) of these trace elements in pre-puberty were: Br—10.5?±?1.3, Fe—28.6?±?4.1, Rb—3.05?±?0.27, Sr—0.42?±?0.08, and Zn—32.9?±?3.2. During puberty and postpuberty, when there is a significant increase in circulating androgens, the mean values were: Br—5.60?±?0.57, Fe—19.3?±?1.6, Rb—3.50?±?0.28, Sr—0.24?±?0.03, and Zn—113?±?10. Mean values (M?±?SΕΜ) of percent volumes (%) of the stroma, epithelium, and lumen in the prostate before puberty were 73.4?±?2.6, 20.4?±?1.7, and 4.45?±?0.94, respectively, versus 46.5?±?2.5, 38.5?±?1.9, and 14.9?±?1.2 during puberty and postpuberty. A significant positive correlation between the prostatic Zn and percent volume of both glandular epithelium (r?=?0.573, p?≤?0.001) and glandular lumen (r?=?0.725, p?≤?0.001) was found. For the first time, it has been demonstrated that the glandular lumen is a main pool of Zn accumulation, and that the stroma is a main pool of Br and Fe accumulation in the normal human prostate, for the age range 14 to 30 years. It was concluded that the Zn binds tightly within the prostatic fluid because the volume of glandular lumen reflects the volume of prostatic fluid.     

Role of estrogens in development of prostate cancer

Estrogens have previously been extensively used in prostate cancer treatment. Serious side effects, primarily in cardiovascular system have, however, limited their use. The therapeutic effect of estrogen in preventing prostate cancer growth was mainly obtained indirectly by feedback inhibition of the hypothalamic release of LRH leading to lowered serum androgen levels and castration like effects. Prostate tissue is also most probably a target for direct regulation by estrogens. Prostate contains estrogen receptor alpha (ERalpha) and beta (ERbeta), which are localized characteristically in stroma and epithelium, respectively. The physiological function of these receptors is not known but there is evidence of the role of estrogens in prostatic carcinogenesis. Developing prostate seems particularly sensitive to increased level of endogenous and/or exogenous estrogens. Perinatal or neonatal exposure of rats and mice to estrogens leads to "imprinting" of prostate associated with increased proliferation, inflammation and dysplastic epithelial changes later in life. Prolonged treatment of adult rodents with estrogens along with androgens also leads to epithelial metaplasia, PIN-like lesions and even adenocarcinoma of prostate speaking for the role of estrogen in prostate cancer development. Recent results concerning antiestrogen inhibition of prostate cancer development beyond PIN-type lesions in transgenic mouse models further suggests a role for estrogens in prostate cancer progression. These results also suggest that direct inhibition of estrogen action at the level of prostate tissue may provide an important novel principle of development of prostate cancer therapies.     

Early changes in the dog prostate after castration. An ultrastructural study

Using electron microscopic techniques the prostate glands of male Beagle dogs were studied 3 days after castration. At this time marked differences in the extent of alterations of the glandular epithelium were observed: Whereas several acini showed only minor changes with reduction of epithelial height and diminution of secretory granules, many acini were severely affected with pronounced alteration of cellular structure and accumulation of large lipid droplets. A constant feature was the stimulation of the basal cells of the grandular epithelium. Additionally, in some areas of the gland aggregations of stimulated basal cells forming an acinus-like structure with a slit-like lumen were found. Our study shows that castration leads to marked alterations of prostatic epithelium within a short time. Androgen deprivation causes regressive changes of secretory epithelial cells, but clearly stimulates the basal cell population.     

Experimental prostate epithelial morphogenesis in response to stroma and three-dimensional matrigel culture.

To reproduce the structural and functional differentiation of human prostatic acini in vivo, prostatic epithelial and stromal cells derived from human primary cultures were cocultured in Matrigel. In the absence of stroma and serum, epithelial spheroids composed of solid masses of stratified and cuboidal cells formed. Outer cells of the spheroid expressed cytokeratins 1, 5, 10, and 14, whereas the inner cells expressed cytokeratin 18. The addition of 2% serum induced formation of a lumen surrounded by a layer of one or two cuboidal and columnar epithelial cells. The further addition of stromal cultures, dihydrotestosterone, and estrogen induced polarization of the epithelium and increased spheroid-forming efficiency. Epithelium expressed either cytokeratin 18 alone or additionally cytokeratins 1, 5, 14, and 10. All spheroid epithelium expressed prostate-specific antigen and prostate-specific membrane antigen. Androgen receptor was only detected in the presence of stroma, serum, and hormones. Thus, development of a functional and morphologically correct prostate gland in vitro is dependent on extracellular matrix, steroid hormones, and factors from stromal cells and serum.     

Stromal-epithelial interactions and heterogeneity of proliferative activity within the prostate

Growth and functional activity within the prostate gland is known to be regulated by androgens whose effects are thought to be mediated via androgen receptors. This concept has been derived in large part through analysis of whole organ homogenates, an approach which ignores potential heterogeneity of biological activity within the gland and the importance of cell-cell interactions. In this review recent findings are summarized which demonstrate that growth of the prostatic ductal network during prepubertal periods, as well as during prostatic regeneration in androgen-treated adult castrates, is nonuniform, with ductal growth being highest at the ductal tips and much lower in proximal ducts closer to the urethra. Androgen dependency for maintenance of ductal architecture following castration follows a similar pattern in that castration results in total destruction of distal ductal architecture, while proximal ducts are maintained albeit in an atrophic state. Thus, striking differences in biological properties are found in distal versus proximal prostatic ducts. Morphogenesis, growth, and secretory cytodifferentiation within the developing prostate is elicited by androgens which act via mesenchymal-epithelial interactions. Through analysis of chimeric prostates constructed with androgen-receptor-positive wild-type mesenchyme and androgen-receptor-negative Tfm (testicular feminization) bladder epithelium, it is now evident that androgenic effects can be elicited in androgen-receptor-deficient (androgen-insensitive) Tfm prostatic epithelium, provided that the connective tissue component of the chimeric prostate is wild type. This observation has been made for both the developing and adult prostate. From this data it is evident that certain androgenic effects (ductal morphogenesis, epithelial growth, and secretory cytodifferentiation) do not require the presence of intraepithelial androgen receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histomorphometric features of ventral prostate in different aged rats after central ghrelin treatment

Ghrelin, the endogenous ligand of growth hormone secretagogue receptor type 1a (GHS-R1a), has emerged as pleiotropic modulator of diverse biological functions, including energy homeostasis and recently, reproduction. The influence of intracerebroventricularly (ICV) administered ghrelin (1 μg/day/rat for 5 days) to rats of different ages, i.e, peripubertal (38 days), adult (60 days) and middle-aged (180 days) on the ventral prostate size and morphology, serum testosterone levels and testis weight was examined. Ghrelin treatment significantly increased (p < 0.05) absolute ventral prostate weight in peripubertal and middle-aged rats, by 27% and 37% respectively, due to enhancement of epithelial and/or luminal compartment of the gland. In adult rats, both absolute and relative volumes of the acinar lumen were significantly decreased (p < 0.05), by 38% and 44% respectively, which was associated with significant increases (p < 0.05) in relative and absolute volumes of interacinar stroma, whereas ventral prostate weigh was unchanged. Irrespective of animal age, ghrelin did not affect serum testosterone levels. These are the first results of ghrelin treatment effects on healthy prostate appearance, which allow us to conclude that the rat ventral prostate response to ghrelin depends on the developmental stage of animals. Our results merit further investigations and may have clinical implications, especially in the light of data on possible role of ghrelin in prostate hypertrophy and adenomas.     

自发性及睾酮诱导犬前列腺增生模型的比较

目的比较自发性及雄激素诱导犬前列腺增生模型的特点,为更好地评价治疗前列腺增生药物奠定方法学基础。方法成年雄性Beagle犬12只,随机分成2组,B超探测符合要求的老年Beagle犬6只,依次设为对照组、睾酮组和老年犬组（即自发性前列腺增生组）。睾酮组动物去势后,经肌肉注射（im）2.5 mg/kg的睾酮,对照组动物给予等体积溶媒,老年犬组动物不给药,连续4周。每周称重一次,最后一次给药24 h后,B超探测前列腺体积,采血,取血清备用。麻醉处死动物,取前列腺,称干湿重,测量前列腺体积,计算前列腺脏器系数,组织切片,HE染色后镜下观察前列腺病理组织学变化,并进一步利用显微图像软件测量前列腺上皮高度及腺腔面积。利用磁酶免和ELISA方法检测血清及前列腺组织中睾酮（T）、双氢睾酮（DHT）、前列腺特异抗原（PSA）和前列腺酸性磷酸酶（PAP）水平。结果①给药后,各组动物体重增长总体呈平稳趋势。②B超结果显示,去势Beagle犬给予睾酮4周,前列腺体积大于对照组（P〈0.01）,老年犬前列腺体积大于成年犬（P〈0.01）。③解剖结果显示,睾酮组和老年犬组实际前列腺体积均明显大于对照组（P〈0.05）,且老年犬前列腺体积大于睾酮组;睾酮组和老年犬组前列腺湿量和脏器系数均大于对照组（P〈0.05）,且老年犬前列腺湿重和脏器系数均大于睾酮组。④病理形态分析显示,睾酮组犬前列腺镜下主要表现为腺体增生,尤其是腺上皮增生,而老年犬则更多表现为间质增生。显微图像分析结果显示,与正常对照组相比,睾酮组前列腺上皮高度增加（P〈0.01）,腺腔面积增大（P〈0.01）;老年Bea-gle犬同样表现为前列腺上皮高度增加（P〈0.01）,腺腔面积增大（P〈0.05）,但上皮高度要低于睾酮组。⑤激素检测结果显示,与对照组相比,睾酮组血清中T、DHT和PAP水平略升高,前列腺组织中T（P〈0.05）、DHT（P〈0.01）、PAP（P〈0.05）和PSA水平升高明显;老年犬血清中T、DHT和PAP水平略升高,前列腺组织中T升高,但DHT、PAP和PSA水平均较正常组为低。结论自发性和睾酮诱导的犬前列腺增生模型均可用于前列腺增生药物评价,但模型间存在一定的差异性。     

Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system

In males, androgens are essential in maintaining the integrity of the prostate. Androgen-ablation induces apoptosis of the prostatic epithelium. In females, ovariectomy induces apoptosis in uterine epithelium while progesterone inhibits this process. The objective of this study was to determine whether androgen and progesterone inhibit apoptosis, respectively, in mouse prostatic and uterine epithelia via steroid receptors in the epithelium or in the stroma. To address this question, prostatic tissue recombinants were prepared with rat urogenital sinus mesenchyme plus bladder epithelium from wild-type or testicular feminization mutant (Tfm) mice. Thus, prostatic tissue was generated having androgen receptor (AR) in both epithelium and stroma or in the stroma only. Castration of hosts induced apoptosis in the AR-negative Tfm prostatic epithelium with an epithelial apoptotic index virtually identical to prostatic tissue recombinants containing wild-type epithelium. Moreover, this castration-induced prostatic epithelial apoptosis was blocked by testosterone and dihydrotestosterone in both wild-type and Tfm prostatic tissue recombinants. Likewise, uterine tissue recombinants were prepared in which epithelium and/or stroma was devoid of progesterone receptor (PR) by using uterine epithelium and stroma of wild-type and PR knockout mice. Progesterone inhibited uterine epithelial apoptosis only in tissue recombinants prepared with PR-positive stroma. The PR status of the epithelium did not affect epithelial apoptotic index. Therefore, the apoptosis in prostatic and uterine epithelia is regulated by androgen and progesterone via stromal AR and PR, respectively. In both cases, epithelial AR or PR is not required for hormonal regulation of epithelial apoptosis in prostatic and uterine epithelium.     

Intravesicular Fas localization in epithelial cells of castrated rat prostate glands

Androgenic steroids regulate the development and size of mammalian prostate epithelial cells. To evaluate the relationship between Fas-Fas ligand system and apoptosis in prostate epithelial cells of the castrated rats, we have examined immunocytochemical localization of Fas antigen in the castrated rat prostate glands at a series of different times. We used a rabbit polyclonal anti-Fas antibody with a streptavidin-biotin method and confocal laser scanning method or an immunogold method. Fas immunolocalization was examined in ventral lobes of prostate glands taken from intact or castrated adult male Wistar rats on day 1, 2, 3, 4 and 5 by light or electron microscopy. At a light microscopic level, the castrated prostate epithelial cells showed mostly Fas immunolocalization in their apical parts of cytoplasm on day 2 after the castration. In addition, their extent of the Fas expression was expanded throughout the cytoplasm in proportion to the androgen ablation periods, and later the Fas expression was detected at luminar or basolateral sides of the epithelial cells. Both immunogold labeling with ultrathin sections and immunoperoxidase technique with cryostat sections demonstrated that Fas was localized mainly in secretory granules of the castrated prostate epithelial cells and some parts of their cell membranes at later stages. Our immunocytochemical findings showed that Fas expression was time-dependently induced in most of the prostatic epithelial cells after castration of rats. The rate of Fas-expressing epithelial cells was too high and inconsistent with the previously reported rate of TUNEL-positive ones. The membrane-associated Fas may have little effect on the apoptosis in the present case, bacause a lot of soluble Fas was secreted from the prostatic epithelial cells. A further study is needed to clarify some significance of the secretory Fas in the prostatic epithelium after the rat castration.     

Role of CEACAM1 and CEACAM20 in an In Vitro Model of Prostate Morphogenesis

CEACAM20, a novel member of the CEACAM1 gene family with expression limited to the lumen of small intestine, testes, and prostate, is co-expressed with CEACAM1 in adult prostate tissue and down-regulated to the same extent as CEACAM1 in prostate cancer. Since prostate cancer often involves loss of epithelial lumen formation, we hypothesized that CEACAM20 and CEACAM1 play important roles in lumen formation of normal prostate epithelium. When prostate cells were grown on Matrigel as a source of extracellular matrix (ECM), they differentiated into acinar structures with single tubules and well-defined lumina closely resembling embryonic prostate organoids. Confocal microscopic analysis revealed restriction of CEACAM20 to acini and CEACAM1 to tubule structures, respectively. Inhibition of CEACAM1 with antibodies or soluble CEACAM1 or antisense oligonucleotides inhibited tubule formation by over 50% while the remaining tubules were stunted. Inhibition of CEACAM20 with antisense oligonucleotides completely inhibited tubule formation and stunted the growth of acini. We conclude that CEACAM20 and CEACAM1 not only mark the lumina of adult prostate tissue but also play a critical role in the vitro generation of prostate organoids.     

Epithelial-stromal transition of MMP-7 immunolocalization in the rat ventral prostate following bilateral orchiectomy

Epithelial cells from involuting rat ventral prostate (VP) express Matrilysin (MMP-7) mRNA. Herein, we investigated by immunohistochemistry the MMP-7 protein location and its association with tissue changes following castration in the VP. Normal and castrated adult male Wistar rats were sacrificed at different times after surgery. VP was examined by immunocytochemistry and immunoprecipitation. Castration promoted a shrinking of prostate ducts with an extensive stromal remodeling. In the VP from normal rats, MMP-7 immunoreactivity was found in epithelial secretory granules. Three days after castration, immunostaining for MMP-7 was found in both the epithelial secretory granules and in the stroma just below the epithelium, mainly at the distal ductal tips. At seven and 21 days after castration, the immunostaining for MMP-7 was found only in the stromal space. Immunoprecipitation confirmed the specificity of the primary antibody by rescuing a pro-enzyme form (28kDa) in the prostate extracts. The present results suggest that MMP-7 participates in the epithelial-stromal interface remodeling of the ventral prostate during the involution achieved by castration, probably in the degradation of components of the epithelial basement membrane.     

Role of stromal tenascin-C in mouse prostatic development and epithelial cell differentiation

Deregulation of epithelial-stromal interactions is considered to play a critical role in the initiation and promotion of benign prostatic hyperplasia (BPH) and prostate carcinoma (PCa). Expression of tenascin-C (TN-C), an extracellular matrix (ECM) glycoprotein, is reportedly higher in BPH and PCa as compared with normal prostate. Remodeling of the ECM alters the homeostatic balance between epithelium and stroma, resulting in physiological changes in cellular functions. To investigate the role of TN-C in prostatic development and differentiation, we evaluated the morphological phenotype of TN-C knockout (KO) mouse prostate (ventral: VP, dorsolateral: DLP, and anterior: AP) and examined tissue recombinants composed of adult mouse DLP epithelium and fetal TN-C KO urogenital sinus mesenchyme (UGM). Histological analysis showed epithelial cell clusters protruding into the ductal lumens in TN-C KO AP and DLP. Interestingly, binucleated cells appeared in epithelium of TN-C KO DLP at 8 weeks. Simultaneously, androgen receptor (AR)-positive cells were decreased in TN-C KO epithelia. Similar to the TN-C KO phenotype, protruded epithelial clusters, binucleated cells, and AR-negative nuclei were induced in DLP epithelium by recombining with TN-C KO UGM. Our results suggest that stromal TN-C might be involved in maintaining epithelial cytodifferentiation, morphogenesis, and androgen receptor expression of normal prostate glands in adult mice.     

Expression of luteinizing hormone and follicle-stimulating hormone receptor in the dog prostate

A possible role for gonadotrophins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the prostate physiology has been suggested in humans and rats. This study aimed at investigating the presence of receptors for LH and FSH (LHR and FSHR) in the canine prostate. Prostates were collected at post mortem from 6 clinically healthy, sexually intact beagles free from any prostatic disorder. Tissue was sampled from dorsal, middle and ventral regions of each prostate. Immunohistochemical localization was performed on wax-embedded sections using polyclonal antibodies for LHR or FSHR. The pattern and intensity of staining in the parenchyma (glandular epithelium) and stroma were determined using a semiquantitative histologic assessment. Receptors for LH and FSH were consistently present in both the glandular epithelium and the stroma in all tissue samples examined. Expression for both receptors was higher in the glandular epithelium than the stroma of all prostatic regions (P < 0.001). In the glandular epithelium, LHR (P < 0.01) and FSHR (P < 0.05) expression was lower in the lateral than the other regions, and there was no difference between dorsal and ventral regions. However, variations in the expression for LHR and FSHR among prostatic regions were not found in the stroma. These findings have demonstrated that LHR and FSHR are expressed in the dog prostate, and the variation observed in their levels of expression among its regions and tissue layers suggests a potential role of gonadotrophins LH and FSH in the regulation of the prostate physiology, particularly the glandular epithelium.