Cholesterol and Testosterone

Posted in General at 11 pm

Taken from BodyBuilding.com:

Testosterone is a 19-carbon steroid hormone produced primarily by the Leydig cells of the testes (in men) and the ovaries (in women). Smaller amounts are produced in the adrenal glands of both sexes. As a “steroid”, testosterone belongs to the androgen class of hormones that also includes dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione, and androstenediol. Six other classes of steroid hormones exist, including estrogens, progestins (some female contraceptives are made of these), mineralocorticoids (which help control water balance), glucocorticoids (mainly anti- inflammatory compounds), vitamin D, and bile acids.

In men, approximately seven mg of testosterone is produced each day, and blood levels range between 300 and 1000 ng/dL (10-28 nmol/L). Females, on the other hand, produce about 1/15th of this amount, leading to average blood levels of only 25 to 90 ng/dL (1 -2.5 nmol/L). All steroid hormones are derived from the sterane ring structure, composed of three hexane (6 carbon) rings and one pentane (5 carbon) ring.

[R: and that’s just to get us started…]

In healthy humans, the “rate-limiting” step in testosterone biosynthesis is the conversion of cholesterol into a hormone called pregnenolone. This hormone is then first converted to either DHEA or progesterone before being further degraded in a stepwise fashion to testosterone. Schematically, the two possible pathways look like this: (Enzymes have been omitted for clarity.)

Cholesterol » pregnenolone » progesterone » androstenedione » Testosterone
Cholesterol » pregnenolone » DHEA » androstenediol » Testosterone

After testosterone is secreted into the bloodstream, 96-98 percent is bound to proteins called albumin and globulin. This binding is thought to serve three purposes: 1) it makes testosterone soluble for transport within the blood, 2) it protects testosterone from degradation by the liver and kidneys, and 3) it serves as a reservoir or storage depot that can be used to dampen fluctuations in plasma testosterone.

The two to four percent not bound to plasma proteins is known as “free testosterone” and is thought to represent the biologically active fraction of the hormone; in other words, the amount that is capable of interacting with cells to cause physiological changes. And although recent data suggest this is most likely an oversimplification, we’ll leave that discussion for another time.

Regulation of testosterone levels is governed by two factors: the total amount of testosterone in the blood, and the binding capacity of the plasma proteins. Obviously, as binding capacity goes up blood levels of free testosterone go down. Not surprisingly, certain drugs (anabolic-androgenic steroids, insulin, etc.) and perhaps nutritional supplements (like avena sativa, urtica dioica, etc.) can reduce the binding capacity of the blood and result in higher free-testosterone levels.

Of the “free” testosterone that interacts at the tissue level, much of it is converted within the cells to DHT – a more potent androgen – by the enzyme 5-alpha reductase. In the prostate, for example, this conversion is thought to be necessary for physiologic effects. Other tissues (like the epididymis, vas deferens, seminal vesicles, skeletal muscle, and bone) lack the 5-alpha reductase enzyme and therefore are thought to respond to testosterone directly.

The conversion of testosterone into estrogens (estriol, estrone and estradiol) is governed by the aromatase enzyme complex and occurs mainly in the liver, brain and fat tissue. Some bodybuilders attempt to avoid / reduce the conversion of testosterone to DHT or estrogens by maintaining low bodyfat and using drugs or nutritional supplements that block 5-alpha reductase and aromatase. Chrysin, saw palmetto and indole-3-carbinol are three examples of legal plant-derived supplements that may maximize testosterone levels by minimizing its conversion to DHT and estrogens. Unfortunately, the bio-availability of many “bioflavanoid” compounds when ingested is poor. Some cutting-edge supplement companies have trick “delivery systems” that attempt to address this problem.

It is important to recognize that blood levels of testosterone – all hormones for that matter – represent a dynamic balance between biosynthesis (which occurs in a pulsatile fashion) and biodegradation. As mentioned, the testes, adrenals and ovaries are responsible for testosterone biosynthesis, while the liver and kidneys are responsible for its biological degradation and excretion. So, for instance, increases in plasma testosterone commonly observed following a hard weight-training session are not just the result of increased production of testosterone from the testes, but also from a reduction in its clearance (blood flow to the liver and kidneys is reduced during exercise). Make sense?

This balance between synthesis and breakdown also make a single blood testosterone value extremely difficult to interpret. As noted decades ago, testosterone levels rise and fall throughout the day; therefore a single testosterone value could represent a peak or valley on the daily testosterone roller coaster.

1 Comment »

  1. John McIntosh said,

    05.01.11 at 6 am

    As the winner of the 2000 Mr. Tampa Bay heavyweight class, this is an excellent article that explains the conversion process.

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