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The prostate gland is one of the sex glands of the male reproductive system (Figure 1.6). The male reproductive system also includes the testes, scrotum, penis, and other accessory ducts and organs, all of which serve to nourish, store and transport sperm.
Figure 1.6 The male reproductive system.
In the adult, the prostate gland is about the size of a walnut and lies immediately below the urinary bladder, surrounding the upper part of the urethra (Figure 1.6). The urethra carries urine from the bladder and semen from the sex glands out through the penis. The main function of the prostate gland is to secrete a milky, alkaline fluid (one of the components of semen) into the urethra at the point of ejaculation. The prostate fluid helps to nourish and protect the sperm during intercourse and forms the main bulk of ejaculate volume.
The prostate gland is comprised of 30–50 glands arranged in acini, which empty into the prostatic urethra, the tube that connects the prostate gland with the bladder urethra (Figure 1.7). The prostate gland is divided into three zones: the peripheral zone, transition zone and central zone (Figure 1.7). The function of these different zones is not clear; however, in the young adult prostate gland, the peripheral zone is composed of 65% of the glandular tissue, the transition zone 10% and the central zone 25%. Most cancers develop in the peripheral zone of the prostate gland. The whole organ is encapsulated in a fibrous prostatic capsule.
Figure 1.7 Structure of the prostate gland
Hormonal environment of the prostate gland
In the adult, prostate gland size is maintained through a homeostatic balance between the process of cell renewal (proliferation) and cell death (apoptosis). This balance is regulated by hormones secreted by the endocrine system, mainly androgens, of which testosterone is the major circulating form.
The hormonal environment of the prostate gland is largely dependent upon the part of the endocrine system that involves the hypothalamic-pituitary- testicular axis.
The hypothalamus, a kidney bean-sized structure in the brain, initiates a series of events that leads to the secretion of testosterone (Figure 1.8). The hypothalamus secretes locally acting luteinising hormone-releasing hormone (LHRH), also known as gonadotrophin-releasing hormone (GnRH), and corticotrophin-releasing hormone (CRH) that act on the pituitary gland to release further hormones.
Figure 1.8 The hypothalamic-pituitary-testicular axis.
Pituitary gland
The pituitary gland is situated at the base of the brain and is attached to the hypothalamus like a cherry on a stalk. In response to the hormones secreted by the hypothalamus, the pituitary secretes luteinising hormone (LH), follicle stimulating hormone (FSH) and adrenocorticotrophin (ACTH). These hormones enter the circulation from where they exert their effects on the testes and adrenal glands.
Testes
The final target organs in the hypothalamic-pituitary-testicular axis are the male gonads, or testes (Figure 1.8). Each testis contains a network of tubules, called seminiferous tubules, that produce sperm. Between these tubules there is a system of Leydig cells. These cells produce testosterone through the enzymatic conversion of cholesterol. FSH acts on the seminiferous tubules to promote sperm production, while LH acts on the Leydig cells to stimulate production of testosterone. The testes produce about 5–10 mg of testosterone each day.
Testosterone is the most important male sex hormone and is responsible for maturation of the genital organs and the development of the male secondary sexual characteristics. The growth and maintenance of the prostate gland is critically dependent upon testosterone – a fact that has great importance for the treatment of prostate cancer.
A small proportion (about 5%) of total plasma testosterone is also produced by the adrenal glands. ACTH stimulates the adrenal glands to produce the adrenal androgens, androstenedione and dehydroepiandrosterone, which are converted into testosterone in peripheral tissues and in the prostate gland.
Negative feedback control
Testosterone controls its own release through a negative feedback effect on the hypothalamic-pituitary-testicular axis (Figure 1.8). When testosterone levels in the bloodstream are raised, the hypothalamus reduces the secretion of LHRH, which inhibits the secretion of LH from the pituitary gland. The overall effect is to reduce the amount of LH acting on the Leydig cells, thus reducing testosterone secretion.
Prostatic cell function
Most testosterone (97%) circulates in the bloodstream bound to one of two proteins, either sex hormone binding globulin (SHBG) or albumin. A small percentage of testosterone (2–3%) remains unbound and it is the unbound form of testosterone that is thought to affect the glandular cells of the prostate gland.
Free testosterone passes through the prostate cell membrane where it is metabolised to DHT by the enzyme 5 alpha-reductase. DHT is 2.5 times more potent as a male sex hormone than testosterone. DHT binds to androgen receptors (AR) within the glandular cells. The complex of AR with DHT then targets, within the cell nucleus, specific DNA sequences known as androgen response elements, that activate cell functions, including growth and proliferation (Figure 1.9).
Figure 1.9 The role of testosterone and DHT in stimulating prostate function.
