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Metabolism of testosterone in the human prostate and seminal vesicles.

Tissue from the normal, hyperplastic and the cancerous human prostate as well as tissue from the human seminal vesicles are capable of metabolizing testosterone in vitro. By incubating minced tissue with 3H-testosterone for 2 hours at 37 degrees C the following radioactive metabolites were identified: testosterone (17 beta-hydroxyl-4-androsten-3-one), androstenedione (4-androstene-3,17-dione), androstanedione (5alpha-androstane-3,17-dione), 5alpha-dihydrostestosterone (17 beta-hydroxy-5alpha-androstane-3-one, DHT), 3alpha-androstanediol (5alpha-androstane-3alpha,17beta-diol), 3beta-androstanediol (5alpha-androstane-3beta-17beta-diol) and androsterone (3alpha-hydroxy-5alpha-androstane-17-one). When normal human prostatic tissue was incubated with 3H-testosterone approximately 40% of the hormone was metabolized and 30-35% of the metabolites were identified as DHT. There were apparently no differences in testosterone metabolism between the dorsal and lateral prostatic lobes. A much lower conversion of 3H-testosterone was observed in the seminal vesicles (24%). The same metabolites were formed by prostatic carcinoma tissue, although distinctive quantitative differences from the normal prostate were observed. Thus, only 23% of the testosterone was metabolized by cancerous tissue of which 15% was present as DHT. The formation of 17-keto metabolites and androstanediols in the prostatic carcinoma tissue was approximately the same as in the normal prostatic tissue. The most extensive metabolism of testosterone was found by incubation of tissue from benign nodular prostatic hyperplasia. About 65% of the testosterone was metabolized, and 40% of the metabolites were identified as DHT. Hyperplastic prostatic tissue also showed a significantly higher formation of 5alpha-androstanedoils and the other tissues examined. The high formation of DHT and 5alpha-androstanediols in benign nodular prostatic hyperplasia in comparison with normal and cancerous prostatic tissue and seminal vesicle tissue might indicate that these metabolites should be studied more closely as possible aetiological factors for prostatic hyperplasia. The very low metabolism of testosterone in prostatic carcinoma tissue should be examined further in relation to tumour differentiation and clinical effect of endocrine therapy.

Adenocarcinoma↗

Role of androgen on blood flow and capillary structure in rat seminal vesicles.

To clarify the effect of androgen on the microcirculation in seminal vesicles of adult Wistar rats, we investigated the organ blood flow and morphological features in the capillaries after castration and subsequent testosterone supplementation. Testosterone (T) was subcutaneously injected every 12 hours after castration and its doses were set to 10(-2), 10(-1), 10(0) and 10(1) mg/kg-body weight (T10(-2), T10(-1), T10(0) and T10(1) groups, respectively). Organ blood flow was measured using laser Doppler flowmetry, and the subepithelial capillaries were analyzed using transmission electron microscopy. The capillaries were morphologically classified into 3 types; oval opened (type 1), intermediate (type 2) and collapsed (type 3), and their luminal areas were measured using a computed image analyzer. The organ blood flow was significantly reduced from 36.3+/-5.1 to 21.9+/-2.7 ml x min(-1)/100 g tissue, and the luminal area of the capillaries was significantly reduced from 9.02+/-1.28 to 4.85+/-0.82 microm2 with the shift of the type 1 and type 2 to type 3 after castration. The reduction of the luminal area and the blood flow reduction, and shift of the capillary type were significantly protected by gradated testosterone supplementation. These results indicate that the maintenance of the blood flow and morphological profiles in capillaries depend on androgen-supplementation levels in seminal vesicles.

Animals↗

Case report: tubercular cold abscess of seminal vesicle: minimally invasive endoscopic management.

BACKGROUND: Tubercular cold abscess of the seminal vesicle is very rare, and only a few cases are reported in literature. Preoperative diagnosis is difficult and to the best of our knowledge has not been reported. CASE REPORT: A 35-year-old man presented with a 7-year history of blood in the semen and a reddish brownish discharge per urethra while defecating. On rectal examination, a soft fluctuant mass was felt above the prostate. Abdominal ultrasonography showed cystic swelling of the right seminal vesicle bulging into the posterior bladder wall. Semen examination showed abundant pus cells and 90% immotile sperm with normal morphology. Acid-fast bacilli were not seen, but acid-fast bacilli were found in a 24-hour urine specimen. Cystoscopy showed tubercles in the urethra and brownish discharge from the orifice of the right ejaculatory duct on per-rectal compression of the mass. The abscess cavity was incised with a Collings' knife. Brownish material was evacuated, and the abscess cavity was seen. An 18F Foley catheter was placed for 3 days. Antitubercular therapy was instituted. Ultrasonography repeated after 3, 25, 45, and 75 days showed gradual regression of the abscess cavity. Semen examination after 75 days was normal, with 75% motility, and cystoscopy 45 days postoperatively showed complete healing of the wound. CONCLUSION: The incision connecting the bladder with the abscess cavity facilitated evacuation of pus and complete resolution of the abscess.

Abscess↗

Gas chromatographic-mass spectrometric analysis of steroids and steroid glucuronides in the seminal vesicle fluid of the African catfish, Clarias gariepinus.

Gas chromatographic-mass spectrometric analysis was carried out to identify steroids and steroid glucuronides in the seminal vesicle fluid of African catfish, Clarias gariepinus, collected in the Hula nature reserve (Israel) during the breeding season. Full mass spectra of 5 beta-pregnane-3 alpha, 17 alpha-diol-20-one and cholesterol were obtained. After treatment with beta-glucuronidase the following steroid glucuronides were determined by full mass spectra of the corresponding free steroids: etiocholanolone, 5 beta-androstane-3 alpha, 17 beta-diol-11-one, 5 beta-pregnane-3 alpha, 17 alpha-diol-20-one, and cholesterol. Furthermore, after selected ion monitoring the following steroids and steroid glucuronides could be detected by the presence of at least two characteristic ions at the expected retention time: 5 beta-androstane-3 beta, 17 beta-diol, 5 beta-androstane-3 alpha, 17 beta-diol, etiocholanolone, 5 beta-androstane-3 alpha, 17 beta-diol-11-one, testosterone, 5 beta-androstane-3 alpha, 17 beta-diol-glucuronide, and testosterone-glucuronide. These results agree with the hypothesis that steroid glucuronides, synthesized by the seminal vesicles, are excreted with the seminal vesicle fluid into the external environment, where they might function as sex pheromones.

Animals↗

Ultrastructural and biochemical studies of guinea pig seminal vesicle during postnatal development and after castration.

Final structural and biochemical probes were combined in a study of guinea pig seminal vesicle epithelium. Tissues from intact neonatal, juvenile, and adult, and castrated adult animals were examined using transmission electron microscopy. Thin sections revealed a general increase in secretory activity during normal development which steadily declined during the 90 days after castration. The ultrastructure of the epithelium from the long-term castrate differed significantly from that of the prepubertal intact animal. Protein content of the seminal vesicle epithelium and epithelial cell number decreased dramatically after castration. Other findings are presented which also indicate that the seminal vesicle epithelial cell of the juvenile animal is different from that of the long-term castrated adult.

Animals↗

Metabolism of polyunsaturated (n-3) fatty acids by monkey seminal vesicles: isolation and biosynthesis of omega-3 epoxides.

Monooxygenases of monkey seminal vesicles can metabolize arachidonic acid (20:4(n-6)) by w3-hydroxylation to 18(R)-hydroxyeicosatetraenoic acid (18(R)-HETE) and eicosapentaenoic acid (20:5(n-3)) to 17,18-dihydroxyeicosatetraenoic acid (Oliw, E.H. (1989) J. Biol. Chem. 264, 17845-17853). The present study aimed to further characterize the oxygenation of (n-3) polyunsaturated fatty acids. 14C-Labelled 22:6(n-3), 20:5(n-3), 20:4-(n-3) and 18:3(n-3) were incubated with microsomes of seminal vesicles of the cynomolgus monkey, NADPH and a cyclooxygenase inhibitor, diclofenac, and the main metabolites were identified by capillary gas chromatography-mass spectrometry. 22:6(n-3) was slowly metabolized to 19,20-dihydroxy-4,7,10,13,16-docosapentaenoic acid, while 20:5(n-3), 20:4(n-3) and 18:3(n-3) were metabolized more efficiently to the corresponding w4,w3-diols. The w3 epoxides, which were obtained from 20:5(n-3) and 18:3(n-3), were isolated in the presence of an epoxide hydrolase inhibitor, 1(2)epoxy-3,3,3-trichloropropane, and the geometry of the epoxides was determined to be 17S, 18R and 15S, 16R, respectively. While 20:5(n-3) was metabolized almost exclusively to the epoxide and diol pair of metabolites, 18:3(n-3) was metabolized not only to the w3 epoxide and the corresponding diol, but also to the w2 alcohol, 17(R)-hydroxy-9,12,15-octadecatrienoic acid. 22:6(n-3) and 5,8,11,14-eicosatetraynoic acid inhibited the biosynthesis of 18(R)-HETE from arachidonic acid (IC50 0.16 and 0.14 mM, respectively). In comparison with 20:4 or 18:3(n-3), 18:1(n-9) and 22:5(n-6) appeared to be slowly metabolized by seminal monooxygenases, while 18:2(n-6) was converted to the w3 alcohol and to smaller amounts of the w2 alcohol (4:1). Together, the results indicate that the w3-hydroxylase and w3-epoxygenase enzyme(s) metabolize 20:4(n-6) and 20:5(n-3) almost exclusively to the w3(R) alcohol and the w3(R, S) epoxide, respectively, while longer and shorter fatty acids either are poor substrates or metabolized with a lesser degree of position specificity.

Animals↗

Quantitative assessment of seminal vesicle and prostate drug concentrations by use of a noninvasive method.

BACKGROUND: The male genital tract is a complex collection of anatomically and biochemically distinct compartments that contribute to the ejaculate. Understanding the pharmacokinetics in these compartments should inform rational therapeutics involving these glands. METHODS: Nineteen men were administered a single dose of 600 mg chloroquine (base) and 975 mg aspirin before providing a semen sample by masturbation with fractionation into a 5-compartment collection device. Fractions were assayed for fructose (unique seminal vesicle marker), prostate-specific antigen (unique prostate marker), salicylate, and chloroquine. Seminal vesicle and prostate concentrations of salicylate and chloroquine were estimated via a novel analytic method involving a multilevel latent-variable model implemented by use of Bayesian methods. RESULTS: The geometric mean chloroquine semen/blood ratio was 4.02 (95% confidence interval [CI], 2.36-6.86); for salicylate, the primary metabolite of aspirin, the semen/blood ratio was 0.10 (95% CI, 0.08-0.14). The estimated mean prostate/seminal vesicle ratio for salicylate, 0.38 (95% CI by Bayesian methods, 0.12-0.73), was consistent with our hypothesis that salicylate would achieve higher concentrations in the seminal vesicle than in the prostate. Chloroquine, however, did not demonstrate a statistically significant seminal vesicle/prostate difference (4.41; 95% CI by Bayesian methods, 0.14-30.52). CONCLUSIONS: We successfully demonstrated the quantitative, noninvasive estimation of drug concentrations in the prostate gland fluid distinct from the seminal vesicle fluid using our optimized method of split-ejaculate collection and a novel mixed-effects model with Bayesian estimation. Our methods can be applied to gland-specific quantitation of drugs and other substances of interest, thus enabling pharmacokinetic, pharmacodynamic, and pathophysiologic studies to inform rational therapeutics within different glands of the male genital tract.

Adult↗

Developmental pattern of androgen-regulated proteins in seminal vesicles from the mouse.

Proteins from secretions or homogenates of mice seminal vesicles were analysed by polyacrylamide gel electrophoresis. In homogenates about 15 bands were differentially induced with molecular weights (MW's) of 12, 13, 14, 15, 15.5, 71, 120 and 140 kD, or repressed molecular weights of 12.5, 14.3, 28, 30, 53, 73, 90-105 kD). The effects of castration were reversed by testosterone and dihydrotestosterone but not by oestradiol, progesterone or corticosterone. When the androgen-dependence of proteins was investigated using radioactive methionine the protein spectra showed that about 12 bands with molecular weights of 13, 13.7, 14, 15, 15.5, 16, 20.5, 24, 37, 38.5, 56, 68, 96 and 180 kD were differentially induced or repressed by androgens. Of the induced proteins, those with low molecular weight (12-15.5 kD) were accumulated in significant amounts between 20 days and 30 days, coincident with the pubertal increase of androgens in the seminal vesicles. Those induced proteins with high molecular weight (71, 120 and 140 kD) appeared between 40 days and 60 days. The androgen-repressed proteins were strongly evident in immature males, but disappeared after day 40.

Aging↗

Structural study of the involution of the seminal vesicles of the guinea pig following orchiectomy.

The involution of the seminal vesicles of the guinea pig after castration has been studied by electron microscopy. The epithelial cells decreased in size and the basal lamina became more tortuous after castration. The most obvious changes occurred in the amount and configuration of the granular endoplasmic reticulum (GER). Besides a general decrease in GER, there was also a change from predominantly parallel arrays to a spiral or concentric arrangement, followed by dilation and vesiculation of the GER. There was an increase in glycogen and lipid contents of the epithelial cells. Large aggregates of glycogen particles were found associating with dilated GER and lipid droplets and these glycogen particles increased with the progression of involution. The Golgi complex became smaller and a slight increase in the number of autophagic and lysosomal granules was observed. Secretory granules decreased in size and quantity but persisted even at 4 months after the operation. The postcastration response of the seminal vesicles of the guinea pig was slow and incomplete and was different from that of the rat and mouse, where involution was virtually completed within 3 weeks. The slow and incomplete regression is not clear, but is believed to be related to the function of the adrenal glands which may provide the extratesticular source of hormone to partially maintain the gland after castration.

Adrenal Glands↗

Soluble proteins of guinea pig seminal vesicle lumen: purification and partial characterization.

Luminal contents of guinea pig seminal vesicle were extracted with 0.154 M NaCl and the soluble protein fraction was studied by DEAE-cellulose and Sephadex G-100 column chromatography; anionic, cationic, and SDS-polyarcylamide disc gel electrophoresis; isoelectric focusing; molecular weight determinations by SDS-polyacrylamide disc gel electrophoresis; analysis for neutral carbohydrate; sucrose density-gradient centrifugation for determination of sedimentation coefficients; and amino acid analyses. Four protein fractions (referred to as proteins 1, 2, 3, and 4 in order to elution) were obtained by DEAE-cellulose column chromatography. Proteins 1, 2, and 4 gave single major bands in multiple disc gel electrophoretic systems. Protein 3 gave one major band and one minor component believed to be a fragment of a primary vesicular protein. Protein 1 is very basic and probably represents the clotting protein of guinea pig semen. The three nonclotting proteins could not be detected in serum and are probably intrinsic to seminal vesicle epithelium. All four proteins were found in animals weighing 700 g or more; only two of the three nonclotting proteins were found in more than half of the younger animals. This makes it even more likely that one or more of the nonclotting proteinc could serve as a useful gene marker in studies of androgen mechanisms.

Amino Acids↗

[Abscess of the seminal vesicle. Clinico-therapeutic review apropos of a case].

Reporting the case of a patient diagnosed with an abscess of the seminal vesicle, treated successfully through parasacral transgluteal percutaneous aspiration lead by computerized axial tomography (CAT). This represents the first case in the literature of percutaneous access to the seminal vesicles through this route. CAT is an effective diagnostic test which makes non-surgical treatment for this type of abscess simpler. A review is made of the literature with regard to the etiology, diagnosis and therapy of seminal vesicle abscesses.

Abscess↗

Binding sites for glucocorticoids in cytosols from the ventral prostate and seminal vesicle of rats.

Binding sites for 3H-dexamethasone (Dex) were demonstrated in cytosols from the ventral prostate and seminal vesicle of rats only if dithiothreitol (DTT) was present in the incubation mixture. The binding observed in the presence of DTT was high affinity (Kd=1-5 nM) and low capacity (Bmax=approx. 0.1 p mole/mg protein) and exhibited a binding specificity for glucocorticoids. The addition of molybdate (Mo) to the incubation mixture enforced the effect of DTT on the binding but the extent of the effect of Mo in cytosols of the ventral prostate differed from that in the seminal vesicle. The binding sites in the cytosols of these tissues were depleted after administration of Dex to animals. The depletion observed was not due to occupation of the binding sites by injected Dex and this was confirmed by the exchange assay. Addition of the cytosol from the seminal vesicle inhibited the 3H-Dex binding in the liver cytosol but the cytosol from the ventral prostate did not show an inhibitory effect. The binding sites in neither of these male accessory sex organs were modified markedly after the animals were castrated. Although the 3H-Dex binding sites observed in the cytoplasm of male accessory sex organs fit the definition proposed for the steroid hormone receptors, it is not clear whether these tissues are under the influence of glucocorticoid or not; the rate of incorporation of 3H-leucine and 3H-orotic acid into the acid-insoluble fraction from the ventral prostate is not influenced by the administration of Dex to animals.

Animals↗

Identification of CYP4F8 in human seminal vesicles as a prominent 19-hydroxylase of prostaglandin endoperoxides.

A novel cytochrome P450, CYP4F8, was recently cloned from human seminal vesicles. CYP4F8 was expressed in yeast. Recombinant CYP4F8 oxygenated arachidonic acid to (18R)-hydroxyarachidonate, whereas prostaglandin (PG) D(2), PGE(1), PGE(2), PGF(2alpha), and leukotriene B(4) appeared to be poor substrates. Three stable PGH(2) analogues, 9,11-epoxymethano-PGH(2) (U-44069), 11, 9-epoxymethano-PGH(2) (U-46619), and 9,11-diazo-15-deoxy-PGH(2) (U-51605) were rapidly metabolized by omega2- and omega3-hydroxylation. U-44069 was oxygenated with a V(max) of approximately 260 pmol min(-)(1) pmol P450(-1) and a K(m) of approximately 7 micrometer. PGH(2) decomposes mainly to PGE(2) in buffer and to PGF(2alpha) by reduction with SnCl(2). CYP4F8 metabolized PGH(2) to 19-hydroxy-PGH(2), which decomposed to 19-hydroxy-PGE(2) in buffer and could be reduced to 19-hydroxy-PGF(2alpha) with SnCl(2). 18-Hydroxy metabolites were also formed (approximately 17%). PGH(1) was metabolized to 19- and 18-hydroxy-PGH(1) in the same way. Microsomes of human seminal vesicles oxygenated arachidonate, U-44069, U-46619, U-51605, and PGH(2), similar to CYP4F8. (19R)-Hydroxy-PGE(1) and (19R)-hydroxy-PGE(2) are the main prostaglandins of human seminal fluid. We propose that they are formed by CYP4F8-catalyzed omega2-hydroxylation of PGH(1) and PGH(2) in the seminal vesicles and isomerization to (19R)-hydroxy-PGE by PGE synthase. CYP4F8 is the first described hydroxylase with specificity and catalytic competence for prostaglandin endoperoxides.

Aryl Hydrocarbon Hydroxylases↗

Histogenesis of induced prostate and seminal vesicle carcinoma in Lobund-Wistar rats: a system for histological scoring and grading.

We have developed a grading system for the evaluation of the histogenesis of neoplastic lesions of the prostate and seminal vesicle of the laboratory rat. Prostatic and seminal vesicle carcinomas were induced in Lobund-Wistar rats by initiation with 30 mg/kg N-nitroso-N-methylurea i.v., followed by promotion with 40 mg testosterone propionate implants 1 week later and at 3-month intervals thereafter. Experimental and control groups were sacrificed at various time points between 5 and 11 months after dosing with N-nitroso-N-methylurea in order to visualize progressive stages of carcinogenesis of the dorsolateral prostate, the anterior prostate, and the seminal vesicle. A system of staging was created which allows three different categories (in situ change, invasion, desmoplasia) of tumor development to be ranked progressively in a manner conducive to nonparametric analysis. Each category was then further subdivided to create a total of six stages. This system can be used to evaluate agents which modify tumor induction or suppression. The application of this staging system to the measurement of the effects of the synthetic retinoid, 4-hydroxyphenyl retinamide, on prostatic carcinogenesis in the Lobund-Wistar rat is described.

Animals↗

A new method to estimate quantitatively seminal vesicle and prostate gland contributions to ejaculate.

AIMS: We sought to optimize a quantitative noninvasive method to determine the concentration in their glands of origin of biochemical markers of compartments of the male genital tract as the first step towards validation of a novel method for estimation of drug concentrations in these male genital tract compartments. METHODS: Sixty-eight men participated. We compared four collection devices to split ejaculate into fractions. Fractions were assayed for fructose and prostate specific antigen (PSA) as unique markers of the seminal vesicle and prostate, respectively. Seminal vesicle fructose and prostatic PSA were estimated using a linear regression method, based on fructose-PSA axis intercepts, and compared with an older method which solves a simultaneous series of equations. RESULTS: A five-compartment collection device performed best with mean (95% confidence interval) PSA vs. fructose r(2) of 0.84 (0.71, 0.98, P < 0.001). Using resampling simulations, glandular PSA and fructose estimates were highly variable and often implausible when using only two fractions. Using our method, the prostate contributed 37-44% to the whole ejaculate and the seminal vesicle contributed 55-61%. The novel regression method was highly correlated (r(2) > or = 0.98) with older methods. CONCLUSIONS: We developed a noninvasive quantitative method of male genital tract biochemical marker estimation using a five-compartment tray to collect three to five ejaculate fractions. Our novel regression method is quantitative and more fully developed than older methods. This noninvasive method for determining glandular marker concentrations should be useful to provide quantitative estimates of drug concentrations in these glands.

Andrology↗

Androgen accumulation andbinding to macromolecules in seminal vesicles: inhibition cyproterone.

Cyproterone reduces the accumulation of testosterone and dihydrotestosterone in seminal vesicles 30 minutes after intravenous administration of tritiated testosterone to castrated rats. Testosterone, added in vitro, binds to macromolecules from the supernatant fraction of the seminal vesicle homogenates; this interaction is antagonized competitively by cyproterone. Cyproterone may diminish androgenic effects by competition for binding molecules.

Animals↗

Cloning and sequence analysis of a cDNA encoding an androgen-dependent mouse seminal vesicle secretory protein.

We report the cloning and sequencing of a new cDNA sequence encoding a protein from the mouse seminal vesicle. An open reading frame of 297 nucleotides encoded a protein of 99 amino acids with a calculated molecular mass of 11.454 kDa. The first 21 amino acids constituted a signal peptide followed by 78 amino acids encoding the secreted protein. The cDNA sequence comprised a 3' untranslated region of 226 bp and the polyadenylation signal AATAAA, 19 bp upstream from the poly(A)+ tail. A high degree of homology was found between this protein and members of the family of seminal vesicle secretory (SVS) proteins, especially rat SVS VI. Northern blot analysis indicated the presence of a 0.7 kb mRNA species in the mRNAs of seminal vesicle tissue. Castration resulted in a marked decrease in the level of the 0.7 kb mRNA encoding the protein, whereas administration of testosterone to castrated males restored the 0.7 kb mRNA.

Amino Acid Sequence↗

The intramural innervation of the human vas deferens and seminal vesicle in infants and children.

Immunohistochemical methods were used to study the autonomic innervation of the vas deferens and seminal vesicle in a series of human postnatal specimens ranging in age from 1 month to 3 years. The occurrence and distribution of nerves immunoreactive for the neuropeptides vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) substance P (SP) and calcitonin gene-related peptide (CGRP) were investigated. In addition immunoreactivity to tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and to protein gene product (PGP 9.5), a general nerve marker were also studied. A neurohistochemical method was used to localise acetylcholinesterase. The results obtained from either organ were similar. Regardless of age, a rich plexus of nerve fibres immunoreactive for PGP 9.5 was present both within the muscle coat and also beneath the epithelium of the vas deferens and seminal vesicle. Some acetylcholinesterase containing nerves occurred in the muscle coat but the majority were found under the epithelium in the connective tissue of the mucosa. TH and DBH-containing nerves (presumably noradrenergic in type) formed dense intramuscular plexuses but none occurred subepithelially. In contrast NPY-containing nerves formed a less dense intramuscular plexus and were also observed beneath the epithelium. Thus while NPY may occur in some of the intramuscular noradrenergic nerve fibres it is clearly not confined to this type of nerve in either the vas deferens or the seminal vesicle. SP- and CGRP-containing nerves were extremely infrequent and, when observed, were confined to the muscle coat.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System↗