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==2001==
===Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma===
Prostate. 2001 Aug 1;48(3):210-24.
Leav I, Schelling KH, Adams JY, Merk FB, Alroy J.
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Corrected and republished from:
Prostate. 2001 May 15;47(3):149-63.
Abstract
BACKGROUND: The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells.
METHODS: Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5alpha-androstane-3alpha diol and estradiol-17alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67.
RESULTS: We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI-67. In contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The numbers of HMC and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR, which suggests that androgens may not be required for the initiation or progression of these cancers.
CONCLUSIONS: Our findings indicate that two biologically distinct populations of basal cells may exist in the canine prostate. In this regard, the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally, we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together, these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development.
Copyright 2001 Wiley-Liss, Inc.
PMID: 11494337
==Gray's Anatomy - The Prostate==
==Gray's Anatomy - The Prostate==
[[File:Gray1160.jpg|thumb|400px|FIG. 1160– Prostate with seminal vesicles and seminal ducts, viewed from in front and above. (Spalteholz.)]]
[[File:Gray1160.jpg|thumb|400px|FIG. 1160– Prostate with seminal vesicles and seminal ducts, viewed from in front and above. (Spalteholz.)]]

Revision as of 16:18, 12 December 2010

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2001

Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma

Prostate. 2001 Aug 1;48(3):210-24.

Leav I, Schelling KH, Adams JY, Merk FB, Alroy J.

Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. Corrected and republished from:

Prostate. 2001 May 15;47(3):149-63. Abstract BACKGROUND: The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells.

METHODS: Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5alpha-androstane-3alpha diol and estradiol-17alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67.

RESULTS: We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI-67. In contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The numbers of HMC and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR, which suggests that androgens may not be required for the initiation or progression of these cancers.

CONCLUSIONS: Our findings indicate that two biologically distinct populations of basal cells may exist in the canine prostate. In this regard, the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally, we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together, these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development.

Copyright 2001 Wiley-Liss, Inc. PMID: 11494337


Gray's Anatomy - The Prostate

FIG. 1160– Prostate with seminal vesicles and seminal ducts, viewed from in front and above. (Spalteholz.)

(Prostata; Prostate Gland)


The prostate (Fig. 1160) is a firm, partly glandular and partly muscular body, which is placed immediately below the internal urethral orifice and around the commencement of the urethra. It is situated in the pelvic cavity, below the lower part of the symphysis pubis, above the superior fascia of the urogenital diaphragm, and in front of the rectum, through which it may be distinctly felt, especially when enlarged. It is about the size of a chestnut and somewhat conical in shape, and presents for examination a base, an apex, an anterior, a posterior and two lateral surfaces.

The base (basis prostatæ) is directed upward, and is applied to the inferior surface of the bladder, The greater part of this surface is directly continuous with the bladder wall; the urethra penetrates it nearer its anterior than its posterior border.

The apex (apex prostatæ) is directed downward, and is in contact with the superior fascia of the urogenital diaphragm.

Surface

The posterior surface (facies posterior) is flattened from side to side and slightly convex from above downward; it is separated from the rectum by its sheath and some loose connective tissue, and is distant about 4 cm. from the anus. Near its upper border there is a depression through which the two ejaculatory ducts enter the prostate. This depression serves to divide the posterior surface into a lower larger and an upper smaller part. The upper smaller part constitutes the middle lobe of the prostate and intervenes between the ejaculatory ducts and the urethra; it varies greatly in size, and in some cases is destitute of glandular tissue. The lower larger portion sometimes presents a shallow median furrow, which imperfectly separates it into a right and a left lateral lobe: these form the main mass of the gland and are directly continuous with each other behind the urethra. In front of the urethra they are connected by a band which is named the isthmus: this consists of the same tissues as the capsule and is devoid of glandular substance.

The anterior surface (facies anterior) measures about 2.5 cm. from above downward but is narrow and convex from side to side. It is placed about 2 cm. behind the pubic symphysis, from which it is separated by a plexus of veins and a quantity of loose fat. It is connected to the pubic bone on either side by the puboprostatic ligaments. The urethra emerges from this surface a little above and in front of the apex of the gland.

The lateral surfaces are prominent, and are covered by the anterior portions of the Levatores ani, which are, however, separated from the gland by a plexus of veins.

The prostate measures about 4 cm. transversely at the base, 2 cm. in its antero-posterior diameter, and 3 cm. in its vertical diameter. Its weight is about 8 gm. It is held in its position by the puboprostatic ligaments; by the superior fascia of the urogenital diaphragm, which invests the prostate and the commencement of the membranous portion of the urethra; and by the anterior portions of the Levatores ani, which pass backward from the pubis and embrace the sides of the prostate. These portions of the Levatores ani, from the support they afford to the prostate, are named the Levatores prostatæ.

The prostate is perforated by the urethra and the ejaculatory ducts. The urethra usually lies along the junction of its anterior with its middle third. The ejaculatory ducts pass obliquely downward and forward through the posterior part of the prostate, and open into the prostatic portion of the urethra.


Structure

The prostate is immediately enveloped by a thin but firm fibrous capsule, distinct from that derived from the fascia endopelvina, and separated from it by a plexus of veins. This capsule is firmly adherent to the prostate and is structurally continuous with the stroma of the gland, being composed of the same tissues, viz.: non-striped muscle and fibrous tissue. The substance of the prostate is of a pale reddish-gray color, of great density, and not easily torn. It consists of glandular substance and muscular tissue.

The muscular tissue according to Kölliker, constitutes the proper stroma of the prostate; the connective tissue being very scanty, and simply forming between the muscular fibers, thin trabeculæ, in which the vessels and nerves of the gland ramify. The muscular tissue is arranged as follows: immediately beneath the fibrous capsule is a dense layer, which forms an investing sheath for the gland; secondly, around the urethra, as it lies in the prostate, is another dense layer of circular fibers, continuous above with the internal layer of the muscular coat of the bladder, and blending below with the fibers surrounding the membranous portion of the urethra. Between these two layers strong bands of muscular tissue, which decussate freely, form meshes in which the glandular structure of the organ is imbedded. In that part of the gland which is situated in front of the urethra the muscular tissue is especially dense, and there is here little or no gland tissue; while in that part which is behind the urethra the muscular tissue presents a wide-meshed structure, which is densest at the base of the gland—that is, near the bladder—becoming looser and more sponge-like toward the apex of the organ.

The glandular substance is composed of numerous follicular pouches the lining of which frequently shows papillary elevations. The follicles open into elongated canals, which join to form from twelve to twenty small excretory ducts. They are connected together by areolar tissue, supported by prolongations from the fibrous capsule and muscular stroma, and enclosed in a delicate capillary plexus. The epithelium which lines the canals and the terminal vesicles is of the columnar variety. The prostatic ducts open into the floor of the prostatic portion of the urethra, and are lined by two layers of epithelium, the inner layer consisting of columnar and the outer of small cubical cells. Small colloid masses, known as amyloid bodies are often found in the gland tubes.

Vessels and Nerves

The arteries supplying the prostate are derived from the internal pudendal, inferior vesical, and middle hemorrhoidal. Its veins form a plexus around the sides and base of the gland; they receive in front the dorsal vein of the penis, and end in the hypogastric veins. The nerves are derived from the pelvic plexus.



Text from Gray's Anatomy

Reference: Gray, Henry. Anatomy of the Human Body. Philadelphia: Lea & Febiger, 1918.


2010

The Effects of Aging on the Molecular and Cellular Composition of the Prostate Microenvironment

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012501

2009

The role of Wnt5a in prostate gland development

Dev Biol. 2009 Apr 15;328(2):188-99. Epub 2009 Jan 14.

Huang L, Pu Y, Hu WY, Birch L, Luccio-Camelo D, Yamaguchi T, Prins GS.

Department of Urology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60614, USA.

Abstract

The Wnt genes encode a large family of secreted glycoproteins that play important roles in controlling tissue patterning, cell fate and proliferation during development. Currently, little is known regarding the role(s) of Wnt genes during prostate gland development. The present study examines the role of the noncanonical Wnt5a during prostate gland development in rat and murine models. In the rat prostate, Wnt5a mRNA is expressed by distal mesenchyme during the budding stage and localizes to periductal mesenchymal cells with an increasing proximal-to-distal gradient during branching morphogenesis. Wnt5a protein is secreted and localizes to periductal stroma, extracellular matrix and epithelial cells in the distal ducts. While Wnt5a expression is high during active morphogenesis in all prostate lobes, ventral prostate (VP) expression declines rapidly following morphogenesis while dorsal (DP) and lateral lobe (LP) expression remains high into adulthood. Steroids modulate prostatic Wnt5a expression during early development with testosterone suppressing Wnt5a and neonatal estrogen increasing expression. In vivo and ex vivo analyses of developing mouse and rat prostates were used to assess the functional roles of Wnt5a. Wnt5a(-/-) murine prostates rescued by organ culture exhibit disturbances in bud position and directed outgrowth leading to large bulbous sacs in place of elongating ducts. In contrast, epithelial cell proliferation, ductal elongation and branchpoint formation are suppressed in newborn rat prostates cultured with exogenous Wnt5a protein. While renal grafts of Wnt5a(-/-) murine prostates revealed that Wnt5a is not essential for cyto- and functional differentiation, a role in luminal cell polarity and lumenization of the ducts was indicated. Wnt5a suppresses prostatic Shh expression while Shh stimulates Wnt5a expression in a lobe-specific manner during early development indicating that Wnt5a participates in cross-talk with other members of the gene regulatory network that control prostate development. Although Wnt5a does not influence prostatic expression of other Wnt morphogens, it suppresses Wif-1 expression and can thus indirectly modulate Wnt signaling. In summary, the present finds demonstrate that Wnt5a is essential for normal prostate development where it regulates bud outgrowth, ductal elongation, branching, cell polarity and lumenization. These findings contribute to the growing body of knowledge on regulatory mechanisms involved in prostate gland development which are key to understanding abnormal growth processes associated with aging.

PMID: 19389372 PMCID: PMC2828764

http://www.ncbi.nlm.nih.gov/pubmed/19389372


Imaging of the seminal vesicle and vas deferens

Radiographics. 2009 Jul-Aug;29(4):1105-21.

Kim B, Kawashima A, Ryu JA, Takahashi N, Hartman RP, King BF Jr.

Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. kim.bohyun@mayo.edu Abstract The seminal vesicle (SV) and vas deferens (VD) are ancillary but essential urogenital organs. Understanding their embryologic features and anatomy can be helpful in evaluating various disorders of these organs. Recently, cross-sectional imaging modalities, including ultrasonography, computed tomography, and magnetic resonance (MR) imaging, have been increasingly used for evaluation of the SV and VD. The development of these organs is closely related to that of urinary organs, including the kidneys and ureters. Frequently, unilateral SV agenesis is associated with renal agenesis, and bilateral SV or VD agenesis is associated with mutations of the cystic fibrosis gene. Congenital SV cysts are commonly associated with ipsilateral renal agenesis or dysgenesis. These congenital anomalies can be well evaluated with MR imaging. Inflammation, post-radiation therapy changes, and amyloidosis of the SV appear as diffuse wall thickening and may mimic tumor invasion by prostate cancer. Primary neoplasms involving the SV and VD are extremely rare, whereas secondary neoplasms are much more common. Carcinoma from the prostate, bladder, or rectum can directly invade the SV and VD. Typical MR imaging findings of such invasion include a low-signal-intensity mass on T2-weighted images or soft-tissue thickening in the SV or VD along with loss of normal architecture.

Copyright RSNA, 2009

PMID: 19605659 http://www.ncbi.nlm.nih.gov/pubmed/19605659 http://radiographics.rsna.org/content/29/4/1105.long


Morphologic variations of the prostatic utricle

Clin Anat. 2009 Apr;22(3):358-64.

Oh CS, Chung IH, Won HS, Kim JH, Nam KI.

Department of Anatomy, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea. changoh@med.skku.ac.kr Abstract Anatomical variations of the prostatic utricle (PU) have rarely been reported despite an understanding of them being required for diagnosing and treating PU anomalies. This study was performed on 57 prostates to clarify the variations of this structure. Fifty prostates were dissected under a surgical microscope, five prostates were used for ultrasonography and dissection, and two others were processed for light microscopy and reconstructed into 3D models. The PU was classified into three types based on the location of its pouch. The most common type was one in which the PU projected out from between the two ejaculatory ducts. The site and shape of the utricular orifice were also diverse on the seminal colliculus, which was most commonly located on the distal three-fourths of the prostatic urethra. The results of this study clarified the variations in the anatomy of the PU and may help improve diagnosis and treatment of PU diseases.

(c) 2009 Wiley-Liss, Inc. PMID: 19173260


2008

Regulation of Epithelial Branching Morphogenesis and Cancer Cell Growth of the Prostate by Wnt Signaling

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002186

2003

Quantification of expression of netrins, slits and their receptors in human prostate tumors

Int J Cancer. 2003 Jan 20;103(3):306-15. Latil A, Chêne L, Cochant-Priollet B, Mangin P, Fournier G, Berthon P, Cussenot O.

UroGene, Génopole, Evry Cedex, France. a.latil@urogene.com

Abstract

Recently, DCC (Deleted in Colorectal Cancer) protein has been forwarded as a receptor for netrin. The Netrin/DCC complex is critical for axon guidance and cell migration. In the developing nervous system, netrin protein secreted by midline cells attracts commissural axons by activating the DCC receptor on growth cones. This attraction can be switched to repulsion or silenced completely, depending on the DCC binding partner. The potential suppressor function of DCC in prostate tumorigenesis, through a still unknown mechanism, prompted us to quantify the expression of several genes involved in this axon guidance pathway. The relative expression levels of DCC, NEO1, NTN1, NTN2L, NTN4, UNC5C, Slit1, Slit2, Slit3, Robo1 and Robo2 were simultaneous quantified in 48 tumors and 7 normal prostate tissues by using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). A reduction in DCC, NEO1, NTN1 and NTN4 expression was observed in prostate tumors, while many of the same prostate tumors over-expressed either Slit genes or their receptors, Robo.

Copyright 2002 Wiley-Liss, Inc. PMID: 12471613


seminal vesicle

Morphology and functions of the human seminal vesicle

Andrologia. 1992 Jul-Aug;24(4):183-96.

Aumüller G, Riva A.

Department of Anatomy and Cell Biology, Philipps University, Marburg, Germany. Abstract The seminal vesicles originate in embryos of about 58 mm crown-rump-length from the Wolffian duct under the influence of testosterone. Along with the ampulla of the vas deferens and the ejaculatory duct, they form a functional unit that develops slowly until the onset of puberty. Developmental malformations occur as uni- or bilateral agenesis, aplasia, cysts, or ureterovesicular fistules. After puberty, the glands form sac-like structures which have a capacity of about 3.4-4.5 ccm and contribute about 70% of the seminal fluid. In addition to secretion, they are capable of reabsorption of fluids or dissolved substances, and of spermatophagy (ingestion and degradation of damaged spermatozoa by epithelial cells). Secretory activity of the glands is a measure of testosterone supplementation to the epithelium. Nervous regulation of secretion is realized by cholinergic post-ganglionic, sympathetic (and perhaps parasympathetic) fibres, derived from pelvic plexus. Contraction of the muscular wall occurs under the influence of excitatory adrenergic and modulatory NPY-encephalin-peptidergic nerve fibres. The secretory products of the seminal vesicles encompass (1) ions (K+: 1.1 mM ml-1) (2) low molecular weight substances (fructose: above 1.2 mg ml-1; prostaglandins above 250 microliters ml-1, (3) peptides (endorphin: 330 pg ml-1), and (4) proteins. In addition to plasma protein related forms such as transferrin, lactoferrin, and fibronectin, specific proteins such as semenogelin (52 kDa) are synthesized, the scaffold protein of semen coagulate forming the substrate for PSA (prostate specific antigen), sperm motility inhibitor (ca. 18 kDa), and others (placental protein 5, protein kinase inhibitor, carboanhydrase, 5'-nucleotidase), some of which are immunosuppressive. Therefore, functions of the seminal vesicles concern (a) formation of seminal coagulum, (b) modification of sperm functions (motility, capacitation), and (c) immunosuppression. Additional functions within the female genital system, perhaps during pre-implantation period, are likely, but remain to be proven experimentally.

PMID: 1642333