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Proliferative pattern of seminal vesicle cells and the production of testosterone and 5 alpha-androgens from birth to adulthood in mice.

Proliferation of seminal vesicle cells and the concentration of testicular and serum androgens (testosterone and 5 alpha-androgens) from birth to adulthood were investigated in mice. The weight of the seminal vesicles increased significantly from day 0 to day 10 after birth (approximately 0.1-1 mg), remained nearly constant in the next 10 days, and increased again (1-50 mg) thereafter. As an index of cell proliferation, two distinct peaks of 5-[125I]iodo-2'-deoxyuridine ([125I]IdUrd) uptake by the whole seminal vesicles were found at days 8 and 30. Types of proliferating cells examined by autoradiography after injection of [3H]thymidine were partially testis-dependent fibromuscular and epithelial cells in the first peak and largely testis-dependent epithelial cells in the second peak. The [125I]IdUrd uptake values found around day 20 and after day 40 were similar to those in neonatally castrated mice. Concentrations of testicular and serum androgens were relatively high on days 8, 30, 35, 40, and 60 (0.2-0.7 ng/mg tissue and 1.3-2.2 ng/ml, respectively) but were very low on day 18 (0.02 ng/mg tissue and 0.4 ng/ml). These findings lead to the hypothesis that androgens secreted from neonatal and prepubertal mouse testes play a major role in the proliferation of seminal vesicle cells and that the quiescent interval of androgen secretion and action occurs around the 20th day after birth in mice.

Aging↗

Fine structure of the seminal vesicle epithelium of the mouse and golden hamster.

The seminal vesicle epithelium of the mouse and golden hamster was examined by light microscopy and by transmission and scanning electron microscopy. By transmission electron microscopy, in the seminal vesicle epithelium of both animals secretory epithelial cells which consisted of mostly light and a few dark cells were observed. The epithelial cells possessed secretory granules which contained a densely stained core. The secretory granules in the mouse epithelium reacted weakly with periodic acid-Schiff (PAS) stain and were slightly stained with alcian blue (AB), and those in the golden hamster exhibited strongly positive reactions with PAS and AB. The nuclei in the mouse tissue were spherical or ovoid, and those in the golden hamster tissue had a few lobes. By scanning electron microscopy, the apical surfaces of most of the epithelial cells were commonly flat or domed, and those of some epithelial cells protruded into the lumen as apocrine-like processes, or possessed small and large orifices. Besides the epithelial cells, there were cells characterized by pseudopodium-like cytoplasmic projections, a few membranous structures, an irregular nucleus, and cytoplasm containing a few dense bodies, in the basal portions of the epithelial cells, or between the basal lamina and the epithelial cells. These cells of the two species were similar in their features.

Animals↗

SSLP-1, a secreted Ly-6 protein purified from mouse seminal vesicle fluid.

The Ly-6 protein family refers to a group of glycophosphatidyl inositol-anchored membrane proteins with ten conserved cysteines. They are thought to be involved in cellular adhesion and signaling. Recently, a subfamily of secreted Ly-6 proteins has been identified. In the present study, we report a secreted Ly-6 protein, secreted seminal vesicle Ly-6 protein 1 (SSLP-1) purified from mouse seminal vesicles using a series of steps including ion-exchange chromatography on a diethylaminoethyl (DEAE)-Sephacel column, gel filtration on a Sephadex G-75 column, and ion-exchange HPLC on a sulfopropyl column. Further analysis demonstrated it to be a novel, previously unnamed, 17 kDa glycoprotein. N-glycosidase F treatment revealed a core protein with a molecular mass of 8720 Da. By Basic Local Alignment Search Tool Protein analysis, we found that SSLP-1 had ten conserved cysteine residues identical with other secreted Ly-6 proteins. The gene Gm191, which is located on chromosome 9, encodes SSLP-1. By Northern blotting with 21 different mouse tissues, we found that Sslp-1 mRNA was predominantly expressed in the seminal vesicle. Immunohistochemistry revealed SSLP-1 protein in the luminal fluid and mucosal epithelium of the seminal vesicles. The amount of Sslp-1 mRNA and SSLP-1 protein in the seminal vesicle was regulated by testosterone and correlated with the stage of animal maturation. The tissue-specific expression pattern suggests that SSLP-1 may play a physiological role in male mouse reproduction.

Animals↗

Growth responses of the guinea pig seminal vesicle epithelium and muscle to long-term treatment with dihydrotestosterone and/or estradiol benzoate.

The three-month treatment regimen with dihydrotestosterone (DHT) and estradiol (E2B) which was capable of producing a supranormal growth of the canine prostate gland equal to that occurring in spontaneous canine benign prostatic hypertrophy, failed to produce similar changes in either the epithelium or smooth muscle of the guinea pig seminal vesicle. The factor limiting the growth response in the seminal vesicle epithelium and muscle of the castrate guinea pig proved to be the lack of a DHT-estradiol benzoate (E2B) synergism, since the growth responses in seminal vesicle tissues to the three-month treatment with DHT alone were similar to that previously recorded for the canine prostate. The lack of a DHT-E2B synergism in the guinea pig seminal vesicle may be responsible for the absence of spontaneous hypertrophy of this organ and other organs such as the human seminal vesicle with advancing age.

Animals↗

Ultrastructure and innervation of water buffalo (Bubalus bubalis) seminal vesicle.

The lining epithelium of secretory end pieces and central glandular duct in the seminal vesicle of the water buffalo (Bubalus bubalis) consists of columnar principal and small polymorphous basal cells. A system of intercellular and even intracellular canaliculi enlarges the secretory surface. The most prominent organelle of the columnar principal cells is the granular endoplasmic reticulum, forming large aggregates of parallel lamellae. Using antibodies against the neural cell adhesion molecule L1 and the neural marker protein gene product 9.5 (PGP 9.5), the innervation pattern of the seminal vesicle becomes evident. The muscular layer surrounding the propria contains a dense network of unmyelinated fibers. Thicker bundles traverse the muscular layer to reach the propria. Around glandular secretory tubules and below the epithelial lining of the glandular duct a tightly woven subepithelial plexus is observed which sends short penetrating branches into the basal zone of the epithelium. These intraepithelial nerves are devoid of Schwann cells and basal lamina (naked axons) and are situated within the intercellular spaces between principal and basal cells. Acetylcholinesterase histochemistry with short (1-2 h) incubation times, dopamine-beta-hydroxylase immunohistochemistry and ultrastructural study of transmitter-containing vesicles was performed. The results suggest that muscular contraction in the seminal vesicle is predominantly under the influence of the sympathetic nervous system, whereas secretory epithelial function is regulated by both sympathetic and parasympathetic fibers.

Acetylcholinesterase↗

Postnatal growth of mouse seminal vesicle is dependent on 5 alpha-dihydrotestosterone.

The seminal vesicles (SV) develop from the lower portion of the Wolffian ducts (WD) in response to androgens, which prevent their degeneration and subsequently stimulate organogenesis of the epididymis, vas deferens, seminal vesicles, and ejaculatory ducts. Earlier studies suggest that testosterone (T) is the active androgen for WD development. By contrast, development of urogenital sinus and external genitalia is dependent upon 5 alpha-dihydrotestosterone (DHT), produced by 5 alpha-reductase within the target tissue itself. To reevaluate the possible role of DHT during SV morphogenesis, SVs from 0-day-old (day of birth) mice were grown for 3, 6, or 9 days in either serum-free or serum-containing medium in the presence or absence of T (10(-7) M) or DHT (10(-8) M). The serum-free medium consisted of Ham's F-12-Dulbecco's Modified Eagle's Medium (1:1) containing insulin, transferrin, cholera toxin, BSA, and epidermal growth factor. The serum-containing medium was Ham's F-12-Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum. Epithelial branching morphogenesis of SVs occurred in serum-free or serum-containing medium supplemented with either T or DHT and was comparable to that of SVs of similar ages in vivo. In serum-containing medium the DNA content of the cultures was about 2-fold higher in T-containing vs. T-deficient medium. However, in serum-free medium the DNA content was the same in cultures grown with or without T. SVs cultured under serum-free conditions in the presence of T plus 390 MSD (17 beta-N,N-diisopropylcarbamoyl-4-aza-5 alpha-androstan-3-one, an inhibitor of 5 alpha-reductase) were completely inhibited in their development, while in the presence of DHT plus 390 MSD, branching morphogenesis was comparable to that in SVs cultured in the presence of T or DHT alone. In medium lacking either T or DHT, SV development was inhibited. In addition, it was confirmed by TLC that [1 beta,2 beta-3H]T was converted into [3H]DHT at the ratio of 15.4% for the first 2 days and at 35.3% for the subsequent 2 days of the culture of SVs in serum-free medium. These data demonstrate that T is important as a precursor of DHT and DHT is the major androgen in the postnatal development of mouse SVs from the lower WD.

Animals↗

Ultrastructural surface alterations of guinea pig seminal vesicle epithelium during postnatal development and after castration.

We have designed a topographic anatomic study using scanning electron microscopy to define surface changes in seminal vesicle epithelium during normal development and after bilateral orchiectomy. Scanning electron microscopy of seminal vesicles from 1-day, 4-week, and 3-month-old intact animals revealed a microvilli-studded luminal epithelial surface with high polyhedral cell profiles extending into the luminal area. Deep furrows outlined all intercellular junctions. Microvilli profiles ranged from short knob-like projections located preferentially along cell margins in 1-day-old animals to 1 mu-long microvilli wih random distribution in mature animals. The most striking finding was that the seminal vesicle epithelium in castrated animals did not revert to the prepubertal state. Rather, cell apices receded from the luminal surface to a level below that of the cell borders and microvilli generally remained somewhat longer in the castrate than in the prepubertal animal. These morphologic findings suggest that the seminal vesicle epithelium in the prepubertal animal and the long-term castrate are quite different.

Animals↗

Morphology of rat prostatic lobes and seminal vesicles after long-term estrogen treatment.

The growth of the prostatic lobes and seminal vesicles of castrated rats was studied morphologically after long-term treatment with estradiol benzoate. Estradiol promoted slightly the growth of the prostatic lobes but more markedly the seminal vesicles, although it had catabolic effects as reflected in low body and levator ani weights. Histologically there was proliferation of the fibromuscular stroma. In the coagulating glands and seminal vesicles there was squamous metaplasia of the epithelium. The histological study also revealed features of special interest, i.e. mucoid epithelium of the coagulating glands. Electron-microscopical and histochemical studies of the mucoid epithelium showed that it had similar characteristics as goblet cells of the intestine of the rat.

Animals↗

Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles.

19R-Hydroxyprostaglandins are major components of human seminal fluid. They are apparently formed in the seminal vesicles by NADPH-dependent omega2-hydroxylation. The hydroxylase is likely a cytochrome P450 (CYP), which has not been identified. To address this issue we studied gene expression of CYPs in human seminal vesicles (n = 4) with reverse-transcription polymerase chain reaction (RT-PCR). CYP1B1, CYP2E1, CYP2J2, CYP3A5, CYP4B1, and CYP4B1 with insertion of three nucleotides (Ser207) were detected in all subjects. RT-PCR with degenerate primers for the CYP4 family yielded a novel cDNA sequence, which was derived from a previously reported genomic sequence on chromosome 19p13.1 and present in all subjects. cDNA cloning showed that the deduced amino acid sequence consisted of 520 amino acids. Northern blot analysis demonstrated mRNA transcripts of approximately 2.1 and approximately 2.3 kb. The deduced protein showed 81.2 and 76.7% amino acid identity with the human enzymes CYP4F2 and CYP4F3. The novel CYP was designated CYP4F8.

Amino Acid Sequence↗

Specific binding sites for [3H]Ro 5-4864 in rat prostate and seminal vesicle.

1. The peripheral-type benzodiazepine receptor was characterized in rat prostate and seminal vesicle using [3H]Ro 5-4864 as radioligand. 2. The affinity of this radioligand for this receptor was higher in rat prostate (KD = 4.36 +/- 1.02 nM) than in seminal vesicle (KD = 8.45 +/- 1.34 nM). 3. The density of binding sites obtained in these two tissues was Bmax = 4164 +/- 873 fmol/mg in prostate and 5978 +/- 1022 fmol/mg in seminal vesicle. 4. The [3H]Ro 5-4864 binding was inhibited non-competitively by atractyloside and alpha,beta-methylene-ATP, suggesting a modulation by the ADP/ATP mitochondrial carrier. 5. Flutamide was able to displace bound [3H]Ro 5-4864 with an IC50 similar to protoporphyrin IX.

Adenosine Diphosphate↗

Transrectal sonography of the prostate and seminal vesicles on patients with hemospermia.

Morphological change of the seminal tract of patients with hemospermia was determined by means of transrectal sonography on 38 patients. Twenty-seven (71%) had positive sonographic findings, including 20 prostatitis and/or seminal vesiculitis, three benigh prostatic hypertrophy, three prostate calculi and one seminal vesicle stone. Simultaneous bacteriologic study revealed positive cultures on 11 patients; 9 of whom (81%) had morphologic appearance on transrectal sonography suggesting inflammatory origin. Our experience indicates that transrectal sonography is capable of surveying the histopathologic change of the prostate and seminal vesicles, and is therefore effective in studying patients with organic hemospermia.

Adult↗

Primary squamous cell carcinoma of the seminal vesicle.

A 69-year-old man with primary squamous cell carcinoma of the seminal vesicle was successfully treated. The patient presented with complaints of gross hematuria and difficulty in urination. Transrectal ultrasonography revealed a cystic mass behind the bladder, and solid tumorous lesions were visualized in the cyst wall by magnetic resonance imaging. The cystic mass was surgically excised and was verified as the enlarged seminal vesicle with concomitant squamous cell carcinoma. The histopathologic diagnosis was squamous cell carcinoma in the seminal vesicle. Postoperatively, 50 Gy of external beam radiation was targeted to the whole pelvic cavity, and the patient was alive without recurrence 2.5 years after surgery. No other neoplasm was discovered in the body.

Aged↗

Endourologic management of seminal vesicle cyst.

Cystic lesions in the region of the seminal vesicles, ejaculatory ducts, or prostate are rare and can be a diagnostic and therapeutic challenge. Open surgery is often necessary for definitive treatment. Recent refinements in transrectal ultrasound imaging and endoscopic instrumentation have expanded the roles of these modalities in the management of retrovesical cysts. We present a case in which a semirigid 6.9F ureteroscope was used to access and drain a seminal vesicle cyst transurethrally, thereby obviating open surgery.

Adult↗

Identification of low density lipoprotein receptor-related protein-2/megalin as an endocytic receptor for seminal vesicle secretory protein II.

The low density lipoprotein receptor-related protein-2/megalin (LRP-2) is an endocytic receptor that is expressed on the apical surfaces of epithelial cells lining specific regions of the male and female reproductive tracts. In the present study, immunohistochemical staining revealed that LRP-2 is also expressed by epithelial cells lining the ductal region and the ampulla of the rat seminal vesicle. To identify LRP-2 ligands in the seminal vesicle, we probed seminal vesicle fluid with 125I-labeled LRP-2 in a gel-blot overlay assay. A 100-kDa protein (under non-reducing conditions) was found to bind the radiolabeled receptor. The protein was isolated and subjected to protease digestion, and the proteolytic fragments were subjected to mass spectroscopic sequence analysis. As a result, the 100-kDa protein was identified as the seminal vesicle secretory protein II (SVS-II), a major constituent of the seminal coagulum. Using purified preparations of SVS-II and LRP-2, solid-phase binding assays were used to show that the SVS-II bound to the receptor with high affinity (Kd = 5.6 nM). The binding of SVS-II to LRP-2 was inhibited using a known antagonist of LRP-2 function, the 39-kDa receptor-associated protein RAP. Using a series of recombinant subfragments of SVS-II, the LRP-2 binding site was mapped to a stretch of repeated 13-residue modules located in the central portion of the SVS-II polypeptide. To evaluate the ability of LRP-2 to mediate 125I-SVS-II endocytosis and lysosomal degradation, ligand clearance assays were performed using differentiated mouse F9 cells, which express high levels of LRP-2. Radiolabeled SVS-II was internalized and degraded by the cells, and both processes were inhibited by antibodies to LRP-2 or by RAP. The results indicate that LRP-2 binds SVS-II and can mediate its endocytosis leading to lysosomal degradation.

Amino Acid Sequence↗

Elimination of stored material from the seminal vesicles of the guinea pig following castration.

Experiments were carried out to determine what factors are involved in the disappearance of stored secretion from the seminal vesicles of the guinea pig and in the concurrent decline in weight of these glands following castration. Seminal vesicles of sexually mature males were unilaterally ligated, and the males were either castrated or left testes intact for a 14-day period. At necropsy, the seminal vesicles were removed and weighed, and biopsies were collected for histological inspection. The weight of nonligated vesicles from castrated males declined to less than half that of ligated sides. In testes-intact males, the weight of ligated vesicles was nearly double that of nonligated vesicles. Epithelial cell heights remained unchanged during the study. The rapid decline in weight of the guinea pig seminal vesicles following castration was attributed to the elimination of stored secretion by way of the urethra rather than by absorption.

Absorption↗

Seminal vesicle involvement after radical prostatectomy: predicting risk factors for progression.

OBJECTIVES: To evaluate and study the factors for progression after radical prostatectomy with seminal vesicle invasion in a cohort of European and American patients. METHODS: The data of 137 patients with isolated seminal vesicle invasion who underwent radical retropubic prostatectomy between 1988 and 2001 were analyzed. The Gleason score of the specimen, presence of capsular invasion, and surgical margin status were noted. Follow-up data were obtained through routine serum prostate-specific antigen (PSA) assays and digital rectal examinations. A defining criterion for progression was a postoperative serum PSA level greater than 0.2 ng/mL or any postoperative radiotherapy or hormonal treatment. Kaplan-Meier analysis was used to determine the actuarial biochemical recurrence-free likelihood, and the log-rank test was used to compare these results. Differences were considered statistically significant when the P value was less than 0.05. RESULTS: After a mean follow-up of 4.9 years (range 0.9 to 13.4), 70 patients (51.9%) had progression. The biochemical 5-year progression-free survival rate was 33.8%. In univariate and multivariate analyses, only preoperative PSA level (P = 0.001) and Gleason score of the specimen (P = 0.01) were independent predictors of progression. Neither capsular invasion nor positive surgical margins predicted progression. When an analysis was performed according to the major Gleason grade of the radical prostatectomy specimen, Gleason grade 5 was associated with a worse prognosis compared with Gleason grade 3 and 4 (P = 0.01). The mean time to progression was 20.5, 17.1, and 10.1 months for Gleason grade 3, 4, and 5, respectively. CONCLUSIONS: Seminal vesicle invasion after radical prostatectomy has historically been associated with a poor prognosis. However, in the present study, seminal vesicle invasion was associated with a 34% rate of freedom from progression at 5 years after surgery alone. Preoperative PSA and Gleason score of the radical prostatectomy specimen were independent factors for progression in the present study, which described the largest patient group to date. The Gleason grade of the radical prostatectomy specimen distinguished among different times to progression.

Aged↗

Expression and pharmacological characterization of alpha1-adrenoceptors in rat seminal vesicle.

In the present study, we investigated the alpha1-adrenoceptor subtypes mediating adrenaline-induced contractions of the rat seminal vesicle by using functional studies. The reverse transcription combined with polymerase chain reaction (RT-PCR) was also used to identify of alpha1-adrenoceptor mRNA subtypes. The rank order of potency of alpha1-adrenoceptor antagonists in blocking the contractile effects of adrenaline was: prazosin = WB 4101 >>> BMY 7378 > chloroethylclonidine, indicating the presence of alpha1A-adrenoceptors in the rat seminal vesicle. In the presence of nifedipine, there was a 76% reduction in the adrenaline-induced contractions. The nifedipine-insensitive component (24%) of the contractile response to adrenaline was unaffected by chloroethylclonidine. A small pool of spare alpha1-adrenoceptors for adrenaline (0.10%) was also detected. All three alpha1-adrenoceptor subtypes were amplified when RT-PCR was performed on total RNA isolated from rat seminal vesicle. In conclusion, these data indicate the presence of three alpha1-adrenoceptor mRNA subtypes, but only alpha1A-adrenoceptors are involved in the rat seminal vesicle contraction.

Adrenergic alpha-Agonists↗