This database concentrates on gene expression during branching morphogenesis. The prostate gland is an example of sex specific androgen regulated development. The text describes human prostate development, though most of the genetic data has been developed using the rodent prostate as a model. Great care must be exercised when comparing late prostatic developmental events between species, though the early events during branching are sufficiently similar to be relevant. The timing of developmental events is imprecise and changes are progressive, the figures given are approximations only and may vary by +/- 10%
The prostate is a fibromuscular exocrine gland. It is a male accessory reproductive gland which expels a complex proteolytic solution into the urethra during ejaculation. The proteolytic enzymes liquify the semen after ejaculation and the phosphatases and salts modify the vaginal environment to enhance sperm survival, though the exact function of many of the components of prostatic secretion have yet to be determined.
The gland surrounds the first 3 cm of the urethra (prostatic urethra) as it leaves the urinary bladder. The ejaculatory ducts enter dorsally and join the urethra within the gland either side of the prostatic utricle. Anatomically, the most caudal aspect of the gland, which apposes the urinary bladder is termed the base of the gland. The walls of the prostatic urethra are highly convoluted and lined with transitional epithelium. In it's resting (not distended) state, the ureter has a longitudinal ridge (the urethral crest) running the length of the gland. The majority of the ductal glands secrete into longitudinal grooves (the urethral sinuses) formed on either side of the ridge. Near the junction of the ejaculatory tubes and the urethra is a short diverticulum in the urethral crest. This is the prostatic utricle, the male vestigial remnants of the female uterus and vagina.
The prostate is covered by a thin vascularised fibrous sheath which surrounds a fibromuscular layer continuous with the smooth muscle surrounding the bladder. The fibromuscular layer extends within the organ as septae, dividing the gland into ill defined lobules and functional areas.
The secretory components of the gland are divided into three concentric layers. The innermost area is comprised of mucosal glands which are concentrated around and secrete into the upper region of the prostatic urethra. The middle or internal area contains submucosal glands which secrete via short ducts into the urethral sinuses. The outer or peripheral area constitutes the majority of the gland and secretes via long ducts into the urethral sinuses. The anterior isthmus is an area of the gland ventral to the urethra, relatively free of glands and rich in fibromuscular tissue.
The prostate is a compound tubuloacinar gland. Within the acini and tubules, the epithelium forms complex folds and papillae supported by a thin highly vascularised loose connective tissue. The secretory epithelium is mainly pseudostratified, comprising tall columnar cells and basal cells which are supported by a fibroelastic stroma containing randomly orientated smooth muscle bundles. The epithelium is highly variable and areas of low cuboidal or squamous epithelium are also present, with transitional epithelium in the distal regions of the longer ducts. Densly packed basal nuclei are characteristic of the prostatic epithelium. The tall columnar secretory cells have an extensive basal golgi complex, apical lysosomes and secretory granules. The epithelium contains scattered neuroendocrine cells, which partly control release and expulsion of prostatic secretions during ejaculation.
The fluid secreted by the prostate gland is rich in acid phosphatase and citric acid. It contains the proteases fibrinolysin and prostate specific antigen (PSA), the enzyme amylase, kallikreins, semenogelin, fibronectin, phospholipids, cholesterol, zinc, calcium and many proteins of unknown function such as beta- microseminoprotein.
At the end of the foetal period, during the seventh week, the male and female urogenital systems are identical. The paramesonephric (Mullerian) ducts, the mesonephric (Wolffian) ducts and the primordial ureters all lead into a rudimentary urinary bladder, which has developed from the urogenital sinus. In the male embryo the paramesonephric ducts degenerate, leaving behind the vestiges of the uterovaginal primordium, the prostatic utricle. The ureters separate from the mesonephric ducts which become incorporated into the urinary bladder and effectively migrate distally to the proximal part of the urethra. The mesonephric duct differentiate to form the ejaculatory ducts.
The first indication of the formation of the prostate is an increase is cellularity of the splanchnic mesoderm surounding the proximal part of the urethra. During week 10, the androgen responsive urogenital sinus mesenchyme induces epithelial buds in the presumptive prostatic urethra. Initially, 14 to 20 solid epithelial buds in at least 5 groups grow into the surrounding mesoderm, this is the presumptive peripheral glandular area. Shortly afterwards a second phase of budding gives rise to the internal glandular area. The solid buds extend and branch under mesodermal control. By the 11th week, lumens form within the epithelial cords and cellular end buds form primitive acini. Mesenchymal cells differentiate into smooth muscle, fibroblasts and blood vesels. During the 12th week, the epithelium continues to proliferate while connective tissue septae extend into the acini, the stroma of the gland thins as the ducts and acini expand.
By 13 to 15 weeks, testosterone concentrations have reached their peak embryonic levels. Androgen mediated epithelial mesenchyme interactions cause the simple cuboidal epithelial cells to differentiate, at first in the proximal regions of the larger ducts then progressing distally. By the end of the 15th week, the secretory cells are functional, the basal cell population has developed and scattered neuroendocrine cells are present. Maturation of the gland continues while embryonic testosterone levels are high, however as testosterone levels fall during the third trimester, the gland enters a quiescent state.
The quiescent state persists until puberty, when testosterone levels again increase and the epithelium proliferates, giving rise to the complex folding seen in the mature gland. The prostate doubles in size during this phase of development, androgen receptors are expressed by the epithelial cells and the full secretory phenotype is established. By 45 to 50 years, testosterone levels are in decline again and the prostate undergoes a period of involution. With increasing age, atrophication of the gland may continue, though commonly, benign prostatic hypertrophy occurs.
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