Chemical structure of testosterone.
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Testosterone

Testosterone is a steroid hormone from the androgen group. Testosterone is secreted in the testes of men and the ovaries of women. It is the principal male sex hormone and the "original" anabolic steroid. In both males and females, it plays key roles in health and well-being. Examples include enhanced libido, energy, immune function, and protection against osteoporosis. more...

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Sources of testosterone

Like other steroid hormones, testosterone is derived from cholesterol. The largest amounts of testosterone are produced by the testes in men, but it is also synthesized in smaller quantities in women by the theca cells of the ovaries, by the placenta, as well as by the zona reticulosa of the adrenal cortex in both sexes.

In the testes, testosterone is produced by the Leydig cells. Due to the dual function of the male gonad, testosterone directly influences spermatogenesis. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone binding globulin (SHBG).

Mechanism of effects

The effects of testosterone in humans and other vertebrates occur 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 cell 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" of the sexually dimorphic areas of the brain by estradiol derived from testosterone programs later male sexual behavior.

Effects of testosterone on humans

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. Anabolic effects include growth of muscle mass and strength, increased bone density and strength, and stimulation of height growth and bone maturation. Virilizing effects include maturation of the sex organs, particularly the penis and the formation of the scrotum in fetuses, and after birth (usually at puberty) a deepening of the voice, growth of the beard and torso hair. Many of these fall into the category of male secondary sex characteristics. Increased testosterone causes deepening of the voice in both sexes at puberty. To take advantage of its virilizing effects, testosterone is often administered to transmen (female-to-male transsexual and transgender people) as part of the hormone replacement therapy, with a "target level" of the normal male testosterone level. And like-wise, male-to-female transsexuals are prescribed drugs to decrease the level of testosterone in the body and allow for the effects of estrogen to develop. Testosterone is also often used by bodybuilders to enhance muscle build.

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When testosterone falls: a hormone deficiency zaps energy and libido. Is supplementing the solution?
From Natural Health, 12/1/05 by Tom Weede

TESTOSTERONE HAS A BIG JOB: It helps maintain a man's libido, sperm production, muscle, and bone. Unfortunately, this hormone often opts for early retirement.

"Testosterone starts dropping from your early 30s, and it's a long, gradual decline over decades," says Ramzi Hajjar, M.D., an associate professor of medicine at Saint Louis University Health Sciences Center.

By age 70, a man typically has half the testosterone he did when he was 30. But some men lose it faster than others, and below-normal levels can occur in your 30s or 40s; type 2 diabetes, HIV, and excess body fat can all lead to deficiencies.

This is serious stuff, considering that low testosterone increases your risk of heart disease, prostate cancer, and Alzheimer's disease, according to Abraham Harvey Kryger, M.D., author of Listen to Your Hormones: A Doctor's Guide to Sex, Love, and Long Life (Especially for Men).

When diagnosing testosterone deficiency, health-care providers look at overt symptoms as well as blood levels. Signs include decreased sex drive, loss of morning erections, lack of energy, weakness, memory problems, and irritability. (Saint Louis University offers a quick quiz to determine if you're at risk; go to slu.edu/adam/maletquiz.pdf.)

The best measure of testosterone is of the amount that is bioavailable, i.e., the testosterone freely circulating in the blood. Free testosterone of less than 70 nanograms per deciliter (ng/dl) is considered abnormal. There are individual variances, so even if you're asymptomatic, checking your testosterone now will help gauge how you're doing down the road.

more hormone

IF YOUR NUMBERS come back low, your doctor may recommend replacement therapy. Patch or gel products are applied to the skin daily, although not all men will have good absorption. Injections every two to three weeks are an effective alternative, and eventually can be done at home. "Treatment restores the level back into a normal range so you have a reversal of symptoms," says Kryger, who has patented a high-potency topical application (wellnessmd.com).

Possible side effects from supplementation include liver complications and blood clots. Also, it's important to be monitored with rectal exams and prostate-specific antigen tests because elevated testosterone can increase the growth and spread of prostate cancer.

What about men with normal testosterone who want a little boost in the weight room or bedroom? The National Institute on Aging maintains that such therapy is "scientifically unproven" for the treatment or prevention of any physical or psychological changes that a man with normal testosterone levels may go through over the years.

The U.S. government recently banned over-the-counter steroid prohormones, except for DHEA (dehydroepiandrosterone), which the body converts into testosterone. "In general, the prohormones are pretty weak," says Robert Tan, M.D., associate professor of internal medicine at Baylor College of Medicine and author of The Andropause Mystery: Unraveling Truths About the Male Menopause. "Very small amounts actually are broken down to form testosterone."

As for natural remedies, research has found that Eurycoma longifolia Jack (aka Tongkat Ali) and Tribulus terrestris, a virility booster used in Ayurveda and Traditional Chinese Medicine, increased the libido of male rats. And a report in the Journal of Exercise Physiology Online found that a formula of zinc, magnesium, and vitamin [B.sub.6] increased testosterone levels and muscle function in college football players.

Compared to direct replacement, however, their role is limited. "They may--if they work at all--increase testosterone by such small amounts, it's clinically and physiologically insignificant," says Hajjar.

Beyond pills and patches, the gym may offer the most natural testosterone enhancer, at least temporarily. In a study published in the Journal of Strength and Conditioning Research, 30 minutes of treadmill running increased testosterone by 27 percent, with levels returning to normal 30 minutes after the run. Seems this is a hormone that could enjoy an active retirement after all.

COPYRIGHT 2005 Weider Publications
COPYRIGHT 2005 Gale Group

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