Testosterone production, action, and clinical manifestations
In the male body, the hypothalamus secretes gonadotropin-releasing hormone, or GnRH, in a pulsatile fashion to stimulate the release of follicle-stimulating hormone, or FSH, and luteinizing hormone, or LH, from the pituitary gland. LH travels in the bloodstream to the Leydig cells of the testes, where it binds to the LH receptor and initiates a series of biochemical events that convert low-density lipoprotein or LDL cholesterol to testosterone. Testosterone secreted from the testes is carried by the bloodstream to target tissues where it produces its biological effects.
Failure of the testes to make physiological levels of testosterone is called hypogonadism. Hypogonadism due to abnormalities of the testes themselves is called primary hypogonadism, whereas a defect in the hypothalamic-pituitary axis is termed secondary hypogonadism. Dual or mixed forms can also occur. If an insufficient amount of testosterone reaches the target tissues, manifestations of testosterone deficiency may appear in the liver, muscle, and adipose tissue. Testosterone binds directly to the androgen receptor. In the liver, testosterone enhances protein synthesis, while in muscle, testosterone enhances muscle mass. Given its role in muscle, men with reduced testosterone levels may complain of muscle weakness, lethargy, or decreased energy.
In other tissues, testosterone must first undergo conversion before becoming biologically active. Testosterone is converted by aromatization to estradiol in the brain and bone, which then binds to the estrogen receptor. Testosterone enhances bone development by promoting bone accretion. Men with reduced testosterone levels may develop osteoporosis. Testosterone acts in the brain to stabilize mood, enhance libido and may even positively affect cognition. As a result, men with testosterone deficiency can experience mood changes, a lack of motivation, and reduced libido. To bind to the androgen receptor on the skin, hair, gonadal, and prostate tissues, testosterone is converted by 5-ᾳ-reductase to dihydrotestosterone or DHT. Testosterone supports the growth of facial, body, axillary and pubic hair in the adult.
However, in some genetically susceptible men, testosterone may also inhibit hair growth in some areas of the scalp, leading to baldness. In the sexual organs, testosterone contributes to penile growth, spermatogenesis, and prostate growth and function. Profound hypogonadism interferes with the vascular function of the penis, or corpora, and may lead to erectile dysfunction and a decrease in orgasm quality. Other effects of testosterone include the promotion of erythropoiesis and the regulation of immune function. In summary, testosterone production plays a key role in many body tissues, and testosterone deficiency can result in myriad clinical manifestations.
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