Clinical Note

Prostate-Specific Antigen (PSA)

One of the proteins whose expression in the prostate is stimulated by dihydrotestosterone is the so-called prostate-specific antigen (PSA), which is found in blood in high concentrations in patients afflicted with prostate cancer. Its abundance in plasma is now widely used diagnostically as a marker of prostate cancer. PSA is a serine protease synthesized in the columnar cells of the glandular epithelium and secreted into the semen. Cleavage of seminogelin by PSA causes liquefaction of the ejaculate and is thought to increase sperm mobility.

target cells

FIGURE 8 Action of testosterone. Testosterone (T) enters its target cell and binds to its nuclear androgen receptor (AR) either directly or after it is converted to dihydrotestosterone (DHT). The thickness of the arrows reflects the quantitative importance of each reaction. The hormone-receptor complex binds to DNA along with a variety of cell specific nuclear regulatory proteins to induce formation of the RNA that encodes the proteins that express effects of the hormone. Not shown: Testosterone may also bind to membrane receptors and initiate rapid ionic changes that may reinforce its genomic effects. Testosterone may also produce rapid changes in cAMP through the binding of the sex-hormone-binding globulin (SHBG) to surface receptors.

target cells

FIGURE 8 Action of testosterone. Testosterone (T) enters its target cell and binds to its nuclear androgen receptor (AR) either directly or after it is converted to dihydrotestosterone (DHT). The thickness of the arrows reflects the quantitative importance of each reaction. The hormone-receptor complex binds to DNA along with a variety of cell specific nuclear regulatory proteins to induce formation of the RNA that encodes the proteins that express effects of the hormone. Not shown: Testosterone may also bind to membrane receptors and initiate rapid ionic changes that may reinforce its genomic effects. Testosterone may also produce rapid changes in cAMP through the binding of the sex-hormone-binding globulin (SHBG) to surface receptors.

and secretion of sebaceous glands in the skin are also stimulated, a phenomenon undoubtedly related to the acne of adolescence. Dihydrotestosterone is the important androgen for recession of scalp hair and stimulation of the sebaceous glands.

Androgen secretion at puberty stimulates growth of the larynx and thickening of the vocal chords, thus lowering the pitch of the voice. Also at this time, the characteristic adolescent growth spurt results from an interplay of testosterone and growth hormone (see Chapter 44) that promotes growth of the vertebrae and long bones. Development of the shoulder girdle is pronounced. This growth is self-limiting, as androgens, after extragonadal conversion to estrogens, accelerate epiphyseal closure (see Chapter 44). Androgens promote growth of muscle, especially in the upper torso. Indeed, men have almost half again as much muscle mass as women. In some animals, the temporal and masseter muscles are particularly sensitive to androgenic stimulation. Growth and nitrogen retention, of course, are also related to stimulation of appetite and increased food intake. Accordingly, androgens bring about increased physical vigor and a feeling of well-being. Testosterone also stimulates red blood cell production by direct effects on bone marrow and by stimulating secretion of the hormone erythropoietin from the kidney. This action of androgens accounts for the higher hematocrit in men than women. In both men and women, androgens increase sexual drive (libido).

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