Testosterone

Testosterone is a steroid hormone from the androgen group. It is the principal male sex hormone and the "original" anabolic steroid.

Testosterone does many things with our innards. It is in significant part responsible for muscle growth. (And, while you might not want to look like Chyna, you probably do enjoy the ability to walk and to sit up on your own, so muscles are a good thing.) It has effects on sexual desire, on mood, on energy levels, and on the nervous system in general. Testosterone is produced by the body through a few different metabolic processes. It is synthesized in two separate places: in the testes, for those who have them, and in the adrenal gland, which pretty much everybody has.

Like other steroid hormones testosterone is derived from cholesterol. The largest amounts of testosterone are produced by testes, but it is also synthesized in smaller quantities by the theca cells of the ovaries, the zona reticulosa of the adrenal cortex, and the placenta. Substantial amounts of the testosterone in women are also produced from estradiol by reverse aromatization in the liver, adipose cells, and other peripheral tissues.

Effects of testosterone in humans and other vertebrates occurs by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about 2.5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects. Androgen receptors occur in many different vertebrate body system tissues, and both males and females respond similarly to similar levels. Greatly differing amounts of testosterone prenatally, at puberty, and throughout life account for a large share of biological differences between males and females.

The bones and the brain are two important tissues in humans where the primary effect of testosterone is by way of aromatization to estradiol. In the bones, estradiol accelerates maturation of cartilage into bone, leading to closure of the epiphyses and conclusion of growth. In the central nervous system, testosterone is aromatized to estradiol. Estradiol rather than testosterone serves as the most important feedback signal to the hypothalamus (especially affecting LH secretion). In many mammals, prenatal or perinatal "masculinization" the sexually dimorphic areas of the brain by estradiol derived from testosterone programs later male sexual behavior.

In general, androgens promote protein synthesis and growth of those tissues with androgen receptors. Testosterone effects can be classified as virilizing and anabolic effects, although the distinction is somewhat artificial, as many of the effects can be considered both. Virilizing effects include growth of the penis, formation of the scrotum, and deepening of the voice, as well as beard and torso hair. Many of these fall into the category of secondary sex characteristics. When they occur to an unwanted degree in women they are termed "virilization" or "masculinization". Anabolic effects include growth of musscle mass and strength, increased bone density and strength, and stimulation of height growth and bone maturation.

Testosterone effects can also be classified by the age of usual occurrence. For postnatal effects in both males and femaies, these are mostly dependent on the levels and duration of circulating free testosterone. The original and primary therapeutic use of testosterone is for replacement in males who lack it (hypogonadism). When used for this purpose, the benefits of body development, physical strength, and mental energy can be dramatic and side effects rare. Testosterone or other anabolic steroids has also been given for many other conditions and purposes besides replacement, with variable success but higher rates of side effects or problems. Examples include infertility, lack of libido or erectile dysfunction, osteoporosis, penile enlargement, height growth, bone marrow stimulation and reversal of anemia, and even appetite stimulation. By the late 1940s testosterone was being touted as an anti-aging wonder drug (e.g., see Paul de Kruif's The Male Hormone) in exactly the same way that growth hormone is being described tody. Anabolic steroids have also been taken to enhance muscle development, strength, or endurance. The latest development in testosterone use appears to be a reprise of the anti-aging claims. A number of physicians, supported by pharmaceutical manufacturers, are populatizing the concept that the testosterone decline of aging (which they term the "andropause") is unnecessary and can be treated. If the usual story plays out, use will increase until large trials demonstrate (1) the benefits are much less dramatic or assured than when treating deficiency, and (2) a higher incidence of side effects will occur associated with this type of use.

Testosterone is the primary androgenic hormone and is responsible for normal growth and development of male sex organs and maintenance of secondary sex characteristics. Pre-pubertal hypogonadism is generally characterized by infantile genitalia and lack of virilization, while the development of hypogonadism after puberty frequently results in complaints such as diminished libido, erectile dysfunction, infertility, gynecomastia, impaired masculinization, changes in body composition, reductions in body and facial hair, and osteoporosis. Hypogonadal men also report levels of anger, confusion, depression, and fatigue that are significantly higher than those reported in eugonadal men.