Adenoid cystic carcinoma of the urethra/Cowper's gland with concurrent high-grade prostatic adenocarcinoma: a detailed clinicopathologic case report and review of the literature.

Primary adenoid cystic carcinoma of the urethra is uncommon with only 9 cases reported in the medical literature; all tumors arose from Cowper's glands. Herein, we report the histological features and immunohistochemical characteristics of 1 patient with primary adenoid cystic carcinoma involving the entire posterior urethra, prostate gland, corpus spongiosum, corpora cavernosa, urogenital diaphragm, perianal soft tissue, and muscularis propria layer of rectum. We also review other published cases to evaluate the prognosis and treatment.

Pharmacokinetic Behaviors of Intravenously Administered siRNA in Glandular Tissues.

The pharmacokinetics of small interfering RNAs (siRNAs) is a pivotal issue for siRNA-based drug development. In this study, we comprehensively investigated the behavior of siRNAs in vivo in various tissues and demonstrated that intravenously-injected naked siRNA accumulated remarkably in the submandibular gland, bulbourethral gland, and pancreas, with a respective half-life of ~22.7, ~45.6, and ~30.3 h. This was further confirmed by gel separation of tissue homogenates and/or supernatants. In vivo imaging and cryosectioning suggested that delivery carriers significantly influence the distribution and elimination profiles of siRNA. Gene-silencing assays revealed that neither naked nor liposome-formulated siRNA resulted in gene knockdown in the submandibular and bulbourethral glands after systemic administration, suggesting that these glands function as drug reservoirs that enable slow siRNA release into the circulation. But robust gene-silencing was achieved by local injection of liposome-encapsulated siRNA into the submandibular gland. Our results enhance understanding of the pharmacokinetic properties of siRNAs and we believe that they will facilitate the development of siRNA therapy, especially for the submandibular gland.

Progesterone receptor up-regulation: a diagnostic tool for the illicit use of oestrogens in adult beef cattle.

The monitoring of gene regulation via mRNA levels to detect anabolic sex steroid administration in cattle is a novel approach to detecting the illicit treatment of livestock in meat production. A previous study revealed that progesterone receptor (PR) gene expression levels were increased in the bulbourethral glands and prostates of 17ß-oestradiol-treated prepubertal calves, suggesting that the PR can be used as a specific molecular biomarker for oestrogen treatment. The aim of this study was to verify the specificity and applicability of the PR to detect the illegal use of 17ß-oestradiol in sexually mature beef cattle. Accessory sex glands were sampled from 42 male beef cattle that were divided into six experimental groups, including two control groups, K1 and K2. Group A cattle were treated with 17ß-oestradiol (five weekly intramuscular doses of 20 mg), and group B cattle were treated with dexamethasone (40 daily doses of 0.7 mg per os). Group C cattle received an implant of Revalor-200 (200 mg of trenbolone acetate and 20 mg of 17ß-oestradiol), and group D cattle received Revalor-200 plus dexamethasone (0.7 mg daily per os). 17ß-Oestradiol, either alone or in combination with other steroids, up-regulated the PR gene and protein expression, even in the absence of detectable histological changes in the accessory sex glands, confirming the high sensitivity of PR gene expression as an indirect diagnostic screening tool to detect illicit oestrogen treatment in sexually mature male bovine.

Anatomical, histological and immunohistochemical study of the reproductive system accessory glands in male viscacha (Lagostomus maximus maximus).

The anatomy, histology and androgen receptor immunohistochemistry of the prostate (P), seminal vesicles (SV), bulbourethral and coagulant gland (CG) were studied in male viscacha, a seasonally reproductive wild rodent. Two histologically well-defined zones, peripheral and central, were identified in the prostate, according to their relationship with the urethra. The epithelial cells were periodic acid-Schiff (PAS)-positive in the central zone and alcian blue negative in the two zones. The SV are a paired gland, tubular, of tortuous aspect and formed by radial layers. The bulbourethral glands were paired, formed by tubuloalveolar acini and surrounded by a thick layer of skeletal muscle. The CG was multilobulated. The large adenomers showed PAS-positive epithelium and were negative to alcian blue. Androgen receptors in the P, SV and coagulating gland showed variations in their distribution with immunohistochemistry heterogeneous pattern. Finally, the reproductive system accessory glands of male viscacha may be considered as a novel and interesting model for the study of seasonal reproduction in photoperiod-dependent animals.

Immunocytochemical localization of MG1 mucin in human bulbourethral glands.

Salivary mucins MG1 and MG2 have been found in the oral cavity where they perform several functions such as the formation of the mucous layer covering the oral mucosa and teeth. Recent studies have demonstrated their presence in other organs and tissues. The aim of this study was to determine their expression in human bulbourethral (Cowper's) glands. Normal bulbourethral glands were obtained at surgery and fixed in a mixture of 1% paraformaldehyde-1.25% glutaraldehyde in 0.1 M cacodylate buffer and embedded in Epon resin. Thin sections were labeled with rabbit antibodies to MG1 or to an N-terminal synthetic peptide of MG2, followed by gold-labeled goat anti-rabbit IgG. The granules of all mucous cells were intensely reactive with anti-MG1, whereas no labeling was detected for MG2. These results indicate that MG1 is not exclusively a salivary component and furthermore show that bulbourethral glands represent a significant source of the MG1 detected in human seminal plasma.

Mature cystic teratoma of the ovary with male accessory sexual glands including seminal vesicles, prostatic tissue, and bulbo-urethral glands: a case report.

We present an extremely rare case of a benign cystic ovarian teratoma with structures of male accessory sexual glands. The patient was a 30-year-old woman. A unilocular cystic tumor, measuring 5 cm in the largest diameter, was found in her right ovary and was removed. The teratoma contained epidermis, skin appendages, respiratory and intestinal epithelia, cartilage, muscle, and nervous and connective tissue. In addition to these histologically mature tissues, there were nodules with prostatic acini, prostate duct-like structures strongly positive for prostate-specific antigen and acid prostatic phosphatase, structures resembling Cowper's glands, and seminal vesicles surrounded by fibromuscular stroma. To our knowledge, this is the first case in the English literature describing seminal vesicles associated with prostatic tissue and bulbo-urethral glands in a mature ovarian teratoma.

[Histochemical analysis of glycoproteins in human bulbourethral glands].

Neutral and acid glycoproteins were detected histochemically in the acinar and ductal cells of the bulbourethral glands. Most of acid glycoproteins in all the glandular cells could be identified as sialomucins. Small amounts of sulfomucins were demonstrated in some secretory acini. Glycogen was not detected in the glands.

[Endocrinocytes of the human bulbourethral glands].

Structure, topography and numbers of endocrinocytes in bulbourethral glands of mature men were studied using immunohistochemical demonstration of chromogranin A. Chromogranin-positive cells were found to be predominantly localized in the epithelium of excretory ducts, while they were sparse in the terminal secretory portions. Endocrinocytes in bulbourethral glands were shown to possess argyrophobic properties and to be stained with antibodies against common cytokeratin. The possibility of epithelial histogenesis of bulbourethral gland endocrinocytes is discussed.

Immunohistochemical localization of androgen receptors in the urogenital tracts of human embryos.

The aim of this study was to investigate androgen receptor (AR) expression in the developing human urogenital tract. The distribution of AR was examined in paraffin-embedded tissue sections of the lower urogenital tract using 55 human embryos of 8-12 weeks of gestation. Immunohistochemistry was performed for AR detection and gender was determined by polymerized chain reaction. There were no differences in the distribution of AR in male and female embryos at any stage of gestation. AR was present only in the mesenchymal tissues of the urogenital sinus at 8 weeks whilst the epithelium was negative, but after 9 weeks the epithelium also showed progressively more positive staining. In the phallus, AR staining was prominent. There was far less staining in the epithelium of the urethral groove from 8 to 10 weeks, whilst the mesenchyme of the urethral folds showed positive staining. At 11 and 12 weeks, both the urethral groove and folds showed uniform staining. The genital tubercle, genital swelling and bulbourethral gland precusors were also positively stained, although paramesonephric ducts were negative. Staining was observed in the mesonephric duct from 9 weeks. There was an absence of staining in the rectum at all stages of gestation. The expression of AR in an epithelium may be dependent upon the mesenchyme. Mesenchymal-epithelial interactions played an important role in development, as has been described in experimental animals. AR expression could play a part in the growth of the genital organs.

Age-related changes in plasma testosterone concentrations and genital organs content of bulk and trace elements in the male dromedary camel.

There is a paucity of information regarding the influence of plasma testosterone concentrations and inorganic cations secreted in the different seminal fractions on the spermatozoon activity throughout the reproductive life of the one-humped camels. To demonstrate these relationships, the genital organs of 12 prepubertal (<3 years), 9 peripubertal (3-<5 years), 16 mature (5-<15 years) and 15 aged (>/=15 years) camels were collected from the Buraidah slaughter house (Al-Qassim Province, Saudi Arabia) during two consecutive breeding seasons (November-April) over 2 years. Plasma testosterone concentrations (mean+/-S.E.) did not exceed 1.4 ng/ml in prepubertal animals with a 3-4 fold increase in peripubertal (3.2+/-0.4 ng/ml) and mature (4.8+/-0.6 ng/ml) camels followed by about 50% decrease (2.6+/-0.3 ng/ml) in aged ones. These hormonal changes were correlated significantly with concentrations of certain elements in the testes (highest Na, Ca and Cu contents), epididymides (highest P and Fe contents), prostate (highest Zn content), and bulbo-urethral glands (highest K and Mg contents). The significance of some interrelationships among the different cations and their biological effects on sperm production and metabolic activity were discussed.

Social effects and boar taint: significance for production of slaughter boars (Sus scrofa).

A study was conducted to elucidate the effects of social factors on the concentrations of boar taint substances, androstenone and skatole, in boars. The factors included dominance (social rank) and the effects of strongly tainted animals on other members of the group. Four successive replicates of 100 pigs (50 boars + 50 gilts) with an average live weight of 24 kg were randomly allocated to 10 pens of 10. Data for this study were collected during the period of 67 to 114 kg of live weight and included the repetitive recording of agonistic behavior during competitive feeding; blood sampling for determination of plasma androstenone, skatole and testosterone in boars; feces sampling for determination of skatole content; and collection of bulbourethral glands in boars, and uteri plus ovaries in gilts at slaughter, for the assessment of sexual maturity. Results show an influence of social rank on plasma concentrations of androstenone (P = .0001) and testosterone (P = .0001), the weight of the bulbourethral glands (P = .0001), and plasma skatole (P = .02). Pens were classified according to the pig with the highest concentration of androstenone in the pen into high, medium, and low maximum pens. In pens with high maximum concentrations of androstenone, the second-highest androstenone concentration (P = .0001), and the average concentration (P = .0003) in the pen were higher than those in pens with medium or low maximum concentrations of androstenone. Mean aggression level was also higher (P = .02), but pens with high maximum aggression level did not have higher mean androstenone concentration. Rank effect on androstenone was more important than aggression effect. Neither maximum androstenone concentration nor maximum aggression level in a pen was related to the pen mean stage of sexual maturity in either sex. No influences of rank, aggression, or aggression received were found on the feces skatole level, and no pheromonal communicative function was demonstrated for skatole. High androstenone concentrations did not have a suppressive effect on androstenone concentrations in other males of the group; on the contrary, the levels were increased. This may be due to a stimulating effect of androstenone and, possibly, mating activity. Consequently, in the production of boars for slaughter, strongly tainted animals should be avoided or removed and mating activity minimized. This could be facilitated by, for instance, slaughtering before sexual maturity or separate rearing of the sexes.

Distinguishing Cowper's glands from neoplastic and pseudoneoplastic lesions of prostate: immunohistochemical and ultrastructural studies.

Mucin-producing Cowper's glands, which are situated in the urogenital diaphragm, can be sampled inadvertently by transurethral resection of the prostate and rarely by needle biopsy. Because they are small, closely packed glandular units, Cowper's glands can be misinterpreted as prostatic adenocarcinoma. A panel of immunoperoxidase and mucin stains performed on 10 Cowper's glands showed negative immunoreactivity for prostatic-specific antigen, prostatic alkaline phosphatase, S-100 protein, and carcinoembryonic antigen. Acini in nine of the 10 Cowper's glands were negative for high-molecular-weight cytokeratin K-903 (34beta E12). One case showed faint focal staining of cells around the periphery of acinar units. Smooth muscle actin consistently stained the periphery of acini in all cases. Ultrastructural examination of one Cowper's gland showed the presence of myoepithelial cells at the periphery of the acini. Contrary to previous reports, the acini were lined by a prominent secretory cell layer underlain by an attenuated myoepithelial cell layer. A negative stain for K-903. without additional immunohistochemical study on Cowper's glands taken during transurethral resection or needle biopsy, may substantiate an erroneous diagnosis of prostatic adenocarcinoma. This potential misdiagnosis of carcinoma can be averted if samples stain positive for mucin and smooth muscle actin and negative for prostate-specific antigen and prostatic alkaline phosphatase.

Fertilization-promoting peptide in reproductive tissues and semen of the male marmoset (Callithrix jacchus).

Fertilization-promoting peptide (FPP) is present in the prostate gland and semen of some mammals, and has been shown to enhance the fertilizing ability of both epididymal mouse and ejaculated human spermatozoa. The novel peptide may prove of importance for the treatment of some cases of male infertility, and a suitable animal model would be useful to test this hypothesis. To this end, we examined reproductive tissues and semen of the male marmoset for the presence of FPP. Peptides were extracted from seminal plasma, testes, prostate, and bulbourethral glands of intact and castrated male marmosets. The peptides were identified by ion-exchange chromatography followed by radioimmunoassay. The mean concentration of FPP immunoreactivity in semen from intact males was 58.7 nM (SE +/- 9.9 nM, n = 10), and anion-exchange chromatography revealed FPP as the only immunoreactive peptide present. Analysis of tissues revealed that FPP in semen was likely to be derived from the prostate gland, which contained this peptide as the major source of immunoreactivity (10.86 pmol/gland; SE +/- 4.39 pmol/gland, n = 4). Only low concentrations of FPP were detectable in the bulbourethral glands, and the peptide was undetectable in the testis. Surprisingly, FPP was readily detectable in the seminal plasma from one castrated marmoset and was present in the prostate gland from 3 castrates at levels which did not differ significantly from those in intact animals (5.47 pmol/gland, SE +/- 1.64 pmol/gland, n = 3). Plasma testosterone measurements indicated that residual circulatory androgens remained after castration, which may be consistent both with the maintenance of mating behavior and the presence of prostatic FPP. We conclude that FPP is present within the prostate gland and seminal plasma of the marmoset at concentrations consistent with a role in male fertility in this species.

Distribution of hyaluronan in bull reproductive organs.

To study the expression of hyaluronan in male reproductive organs and the origin of seminal plasma hyaluronan, we stained various parts of the bull reproductive tract for hyaluronan using a biotinylated probe derived from cartilage proteoglycan (bHABC). The potential loss of hyaluronan during tissue processing was checked with a novel technique by blotting frozen tissue sections on nitrocellulose and staining the blots with bHABC. In the same tissues the CD44 receptor was visualized by Hermes 1 antibody. The testes showed only traces of hyaluronan, whereas both the epithelium and the connective tissue of seminal vesicle, prostate, Cowper's gland, and epididymis were positive in bHABC staining. Hyaluronan was localized on the basolateral surfaces of these epithelial cells. The secretions inside the seminal vesicle and in the ducts of prostate and Cowper's gland were HA-positive, whereas the luminal contents of seminiferous tubules and epididymis were unstained both in paraffin sections and in the in situ blocks. The data indicate that hyaluronan in seminal plasma originates from the accessory sex glands. The co-localization of CD44 with hyaluronan in the basolateral surfaces of the accessory gland epithelia and its absence from other epithelia with little or no hyaluronan supports its role as a hyaluronan receptor.

Immunohistochemical localization of prostate-specific markers within the accessory male sex glands of Cowper, Littre, and Morgagni.

OBJECTIVES: The aim of the study was to explore possible production of prostate-specific markers by the embryologically and physiologically related accessory male sex glands, other than the prostate. METHODS: The accessory male sex glands of Cowper, Littre, and Morgagni were studied systematically in 10 whole-mount autopsy and 5 surgical cystoprostatourethrectomy specimens. Immunohistochemistry was applied with the avidin-biotin-peroxidase method and commercially available monoclonal antibodies raised against prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP). RESULTS: All specimens showed clear microscopic identification of these glands except for Cowper's glands, which were not found in most of the surgical cystoprostatourethrectomy specimens but were found coincidentally in one. Localization of the prostate-specific markers PSA and PSAP was demonstrated for the first time in three Cowper's glands, but they were a consistent finding in Littre's and Morgagni's glands when immunohistochemical identification was performed in a systematic fashion. CONCLUSIONS: PSA and PSAP are mostly produced by prostatic tissue, but not exclusively. These findings may have an impact on the specificity and sensitivity of PSA serum levels after radical prostatectomy because they support the hypothesis of extraprostatic sources of PSA.

Diffuse lymphoid tissue associated with the human bulbourethral gland. An immunohistologic characterization.

This study investigates the presence and distribution of immunocompetent cells in bulbourethral glands obtained from four multiorgan transplant donors. Monoclonal antibodies reacting with B (Leu 12+) and T (Leu 4+) cells, suppressor-cytotoxic cells (Leu 2+), helper-inducer (Leu 3a+) and natural killer (Leu7+) phenotypes, monocyte-macrophages, (LeuM3+), and cells expressing interleukin-2 receptor and HLA-DR antigen were tested in all specimens using an indirect immunoperoxidase staining procedure. T lymphocytes were estimated to represent 10% of the mucosal cell population. Almost all intraepithelial lymphocytes were suppressor-cytotoxic (CD8+) cells. The results demonstrate the presence of a defined distribution of immunocompetent cells in these sex accessory glands. Their role in combatting infections or other chronic genitourinary diseases is still undefined.

Basal cells of H-Dunning tumor are myoepithelial cells. A comparative immunohistochemical and ultrastructural study with male accessory sex glands and mammary gland.

Recent immunohistochemical studies have shown that basal cells in human prostatic epithelium are not myoepithelial cells. Since in the literature the Dunning tumor, originally described as a rat prostate carcinoma derived from the dorsolateral prostate of a Copenhagen rat, was reported to have myoepithelial cells, a comparative immunohistochemical and ultrastructural study was performed in the H-, HIF- and AT3-lines of the Dunning tumor, the male accessory sex glands (ventral, dorsal, lateral prostate, coagulating gland, bulbourethral gland) and the mammary gland of both Copenhagen and Wistar rats. Mono- and polyclonal antibodies directed against intermediate filament proteins (cytokeratin, desmin, vimentin) and the contractile proteins (alpha-actin, muscle type specific myosin, tropomyosin) were used along with phalloidin decoration of F-actin. As in the human prostate, none of the rat prostate lobes in either strains did contain basal cells expressing cytokeratin along with alpha-actin, myosin and tropomyosin Cells representing fully differentiated myoepithelial cells, however, were present as anticipated in the mammary gland, the bulbourethral gland and the H-tumor line of the Dunning tumor. This finding is difficult to reconcile with the contention of a prostatic origin of the H-Dunning tumor. Further studies are required to classify the epithelial parental tissue in order to define the true origin of the H-Dunning tumor and the tumor lines derived thereof.