Testosterone Biochemistry

Biosynthesis

Like other steroid hormones, testosterone is derived from cholesterol (see figure to the right). The first step in the biosynthesis involves the cleavage of the sidechain of cholesterol by CYP11A, a mitochondrial cytochrome P450 oxidase with the loss of six carbon atoms to give pregnenolone. In the next step, two additional carbon atoms are removed by the CYP17A enzyme in the endoplasmic reticulum to yield a variety of C19 steroids. In addition, the 3-hydroxyl group is oxidized by 3-β-HSD to produce androstenedione. In the final and rate limiting step, the C-17 keto group androstenedione is reduced by 17-β hydroxysteroid dehydrogenase to yield testosterone.

The largest amounts of testosterone (>95%) are produced by the testes in men. The male generative glands also contain Sertoli cells which require testosterone for 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).

Regulation

In males, testosterone is primarily synthesized in Leydig cells. The number of Leydig cells in turn is regulated by luteinizing hormone (LH) and follicle stimulating hormone (FSH). In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH which regulates the expression of 17-β hydroxysteroid dehydrogenase.

Environmental factors affecting testosterone levels include:

  • Loss of status or dominance in men.
  • Implicit power motivation predicts an increased testosterone release in men.
  • Aging reduces testosterone release.
  • Hypogonadism
  • Sleep (REM dream) increases nocturnal testosterone levels.
  • Resistance training increases testosterone levels, however, in older men, that increase can be avoided by protein ingestion.
  • Zinc deficiency lowers testosterone levels but over supplementation has no effect on serum testosterone.
  • Licorice. The active ingredient in licorice root, glycyrrhizinic acid has been linked to small, clinically non-significant decreases in testosterone levels. In contrast, a more recent study found that licorice administration produced a substantial testosterone decrease in a small, female-only sample.

Metabolism

Approximately 7% of testosterone is reduced to 5α-dihydrotestosterone (DHT) by the cytochrome P450 enzyme 5α-reductase, an enzyme highly expressed in male accessory sex organs and hair follicles. an enzyme expressed in the brain, liver, and adipose tissues.

Further Reading


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Comments
  1. Hamed Mohammadi Hamed Mohammadi Iran says:

    Hello, thank you for useful informations.
    i need to know that the biochemical structure of testosterone in humans and birds(avian) is the same?
    may you give me a reference?
    thanks in advance

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