Physiology, function (anatomy, embryology)

The sexual accessory glands
The sexual accessory glands consist of the seminal vesicles, the prostate, and Cowper's glands (Fig. 1). They are involved in maintaining the viability and motility of the sperm and in assuring the successful transfer of the sperm to the female system, ultimately to fertilize the ovum. Over 95% of the ejaculate volume originates from the sex accessory tissues and not from the testes, as is often mistakenly believed. A human male's ejaculate volume is about 3 ml and ranges from 2 to 6 ml. Of the 3 ml of an ejaculate, a very small proportion, 0.2 ml, originates from the bulbourethral gland (Cowper's gland) and 0.5 ml from the prostate gland. The largest portion, approximately 2 ml, is secreted from the seminal vesicles and appears in the latter portion of the ejaculate volume. These exocrine glands that form the ejaculate are located at the base of the bladder and empty their secretions directly into the urethra at the time of ejaculation. The growth of these glands and their secretory activity require androgen production from the testes as well as a functioning androgen receptor within the cells of the sex accessory tissues. Removal of testicular function by castration, drug action or failure of the hypothalamic-pituitary-testicular axis will result in diminished circulation of androgens in the serum. As a consequence, the sex accessory tissues will involute and markedly shrink in size and function thus drying up the ejaculate.

In the normal male, the ejaculate is a rich source of proteins and enzymes (20-40 mg/ml), as well as highly bioreactive components such as prostaglandins (200 mug/ml), citrate ion (4 mg/ml), spermine (3 mg/ml) and fructose (2 mg/ml). The term prostaglandins is a misnomer since these compounds are primarily derived from the seminal vesicles, which also produce fructose. The prostate gland contributes high concentrations of citric acid, as well as spermine, a very basic organic molecule of unknown function. The proteins from the seminal vesicle cause the ejaculate to clot and form a coagulum within a few minutes after ejaculation. Subsequently, a serine protease called prostatic specific antigen, secreted from the prostate, lyses the clot. In rodents, a hard elastic plug is formed and it is thought that the slow release of sperm from the coagulum and copulatory plug reduces reflux of sperm from the female tract. Other proteins from the sex accessory tissues coat the sperm and are believed to protect sperm from environmental shock and agglutination, and to mask sperm antigens from the female's immune system. Other proteolytic enzymes in the secretions help sperm traverse cervical mucus, while the prostaglandins stimulate the female reproductive system to transport the sperm toward the ovum. A cascade of activation of proteases and cell signalling pathways is now being studied to resolve how the sex accessory secretions work in temporal concert to assist the sperm to fertilize the ovum.

Structure of the prostate gland
So what is the prostate? It is a small gland the size of an English walnut and normally weighs 25g. The gland is located at the base of the bladder and surrounds the urethra (Fig. 1). The vas deferens, a muscular tube carrying the sperm from the testes, joins the duct from the seminal vesicles, now becoming the ejaculatory duct, and then immediately courses through the structure of the prostate to deposit the sperm and seminal vesicle fluid into the urethra, at the center of the prostate gland. The ejaculatory ducts enter the urethra at the verumontanum. In the urethra, just beyond the verumontanum, the ducts of the prostate appear allowing direct entry of the prostate secretions. There are 15-30 excretory ducts from the prostate entering the urethra as it passes through the prostate. This part of the urethra is called the prostatic urethra. Each of these excretory ducts receives prostatic secretions from 4-6 prostatic lobules that contain prostatic acini surrounded by tall columnar epithelium. It is the acinar glands that respond to androgen stimulation by producing secretory proteins which are stored as viscous secretions in the ascinar spaces. During ejaculation, nerves to the prostate from the hypogastric plexus, under sympathetic stimulation, cause muscular contraction of the prostate and excretion of the ascinar contents into the ducts and out through the urethra and penis to form the ejaculate.
Role of androgens in the prostate

Androgens control the growth of the prostate and formation of the prostatic secretions. Testosterone, synthesized in the Leydig cells of the testes under luteinizing hormone (LH) stimulation, enters the serum, is complexed to a steroid binding globulin and is transported to the prostate. The free testosterone, in equilibrium with its bound and free form in the serum, then diffuses across the epithelial and stromal cell membranes and enters the prostatic cells (Fig. 2). The testosterone is then metabolized to a more androgenic substance called dihydrotestosterone (DHT) through reduction of a double bond at the 5-position of testosterone. The enzyme, termed 5-alpha reductase, forms the more potent DHT which then binds in a highly specific manner to the androgen receptor within the cell. The DHT-bound androgen receptor attaches to a promoter area on DNA at a sequence called the androgen responsive element (ARE). This binding participates in androgen-induced expression of genes such as prostatic specific antigen. In addition, growth factors and their receptors can be induced by DHT and there is much crosstalk between the epithelial cells that form the secretions and their surrounding stromal (connective tissue) cells (Fig. 3). Short range cell-cell interactions mediated through growth factors are termed paracrine effects and this is an important pathway for the exchange of stromal-epithelial interactions. The stromal and epithelial cells also excrete highly insoluble components forming the extracellular matrix and basement membrane that creates a physical interface and solid state support between the prostate epithelial and stromal components. The cooperation and integration of these systems during development, growth, function and pathology of the prostate is a most active area of research. We also await the definition of precise mechanisms by which the prostate influences fertility.

Prostate gland disease
The bad news is that the prostate is probably the leading gland in the American male for causing medical problems. One of four males will be operated on some time in their lifetime to surgically relieve benign prostatic hyperplasia (BPH) that compresses the urethra and produces urinary outflow obstruction. BPH-related operations, most commonly a transurethral resection of the prostate (TURP), are the second leading cause of surgery in males (400,000/yr)in the United States, second only to cataract operations. Far more serious is the high incidence of malignant growths in the prostate gland. Prostate cancer is the leading cause of cancers diagnosed in the American male, now exceeding even lung cancer. The diagnosis of prostate cancer is being aided by detecting the presence of the prostatic specific antigen (PSA) protein in serum. This protein from the prostate is in high concentrations in the ejaculate (1-2 mg/ml) and, when the prostate is damaged by abnormal growth of BPH or cancer, the PSA protein inadvertently enters the serum where detection of greater than 4 mg/ml, indicates a prostate problem such as BPH or cancer.

Suggested Reading

Luke MC, Coffey DS. Male Sex Accessory Tissues Structure, Androgen Action, and Physiology. In: Knobil E, Neill JD, eds. The Physiology of Reproduction, 2nd edition. New York: Raven Press; 1994.