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  Oct 17, 2018

Testosterone Biochemistry

Testosterone is the most important male hormone and is responsible for the changes boys go through to become men as they go through puberty. Testosterone is mostly produced in the testes and a small amount is produced by the adrenal glands. In women, the ovaries also produce a small amount.

Testosterone is one of the steroid hormones and is therefore derived from cholesterol. Some of the steps in the synthesis of testosterone include breaking off or cleavage of the side chain of cholesterol by the mitochondrial cytochrome P450 enzyme, CYP11A. This causes the cholesterol to lose 6 carbon atoms to give pregnanolone.

Next, the CYP17A enzyme present in the endoplasmic reticulum removes two more carbon atoms to give various C19 steroids.

Oxidation of the C19 steroid's 3-hydroxyl group gives androstenedione.

The next step is a vital one and is termed a rate-limiting step. A rate-limiting step is a stage which, if blocked, prevents the synthesis of a compound. In this case, the 17 carbon ketone group androstenedione is reduced by 17-β hydroxysteroid dehydrogenase to produce testosterone.

Regulation of synthesis

In males, testosterone is primarily synthesized in the Leydig cells of the testes.

The pituitary gland in the brain secretes hormones called luteinizing hormone (LH) and follicle stimulating hormone (FSH) which regulate the number of Leydig cells in the testes. Also, LH controls how much testosterone the Leydig cells produce by regulating the expression of 17-β hydroxysteroid dehydrogenase. Since this enzyme mediates the rate-limiting step of testosterone synthesis, its inhibition can stop the synthesis of testosterone.

Examples of factors that reduce testosterone secretion in men include aging, hypogonadism (underactive reproductive organs), weight gain and zinc deficiency.

At least 95% of testosterone synthesis takes place in the male testes. The testosterone acts upon the Sertoli cells in the testes which produce sperm in a process called spermatogenesis. Testosterone is carried to target cells by the bloodstream in which it is mostly bound by the plasma protein sex hormone binding globulin (SHBG).