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FORMATION OF STEROID HORMONES
- May 15, 2018 -

Sources of steroid hormone formation in the body can be divided into two types. One source is the endocrine glands. In women, they include the adrenals, ovaries, and placenta, which is an incomplete endocrine gland. In men, the endocrine glands include the adrenals and testes. A second source of steroid hormones in the body is peripheral tissues. These are nonendocrine tissues such as the liver, intestine, fat, skin, kidneys, and brain.

 

Table 1. Sources of steroid hormones


Endocrine Glands
 In women: adrenals, ovaries, and placenta (incomplete)
 In men: adrenals and testes
Peripheral (Nonendocrine Gland) Tissues
 Splanchnic, e.g., liver, intestine
 Extrasplanchnic, e.g., fat, skin (sexual and nonsexual), kidneys, brain, etc.

 

The first steroidal precursor for biosynthesis of steroid hormones in the adrenals, ovaries, and testes is cholesterol. In these endocrine glands, cholesterol can be synthesized de novo from acetate by a complex series of reactions. Alternatively, it can be obtained directly from circulating low-density lipoprotein (LDL) cholesterol.

Cholesterol can be converted to a variety of steroid hormones in the endocrine glands through the action of specific enzymes, encoded by different genes. The first and rate-limiting reaction in the formation of steroid hormones is the conversion of cholesterol to pregnenolone, which is stimulated by adrenocorticotropin hormone (ACTH) in the adrenals and by LH in the ovaries and testes. This reaction is complex and occurs in the mitochondria. It is catalyzed by the enzyme C20-22-lyase (also referred to as C20-22-desmolase), which is encoded by the CYP11A gene. A key step in the reaction is the transport of cholesterol from extracellular sources to the inner mitochondrial membrane, and subsequent loading of the precursor into the active site of the enzyme. Intramitochondrial cholesterol movement appears to involve coordinated activation of the steroidogenic acute regulatory (StAR) protein and peripheral-type benzodiazepine receptor.12 Both the delivery of cholesterol to the enzyme and the enzyme level are primarily under the control of tropic hormones (LH or ACTH) using cyclic AMP or calcium as the intracellular messenger. Once pregnenolone is formed, it can then be converted to progesterone, androgens, estrogens, and corticosteroids. For this reason, pregnenolone is sometimes referred to as the “mother” steroid.

Although the adrenals, ovaries, and testes can all synthesize androgens, only the adrenals produce corticosteroids. The ovaries and testes, but not the adrenals, can form estrogens. This does not mean that the adrenals, ovaries, and testes lack the enzymes to synthesize estrogens, or corticosteroids. This is evident in feminizing adrenal tumors, which produce estrone and estradiol in high amounts, and in testicular and ovarian tumors that produce certain corticosteroids. Thus, it appears that the activity of certain steroidogenic enzymes in the adrenals, ovaries, and testes are suppressed by mechanisms that are not yet understood.

The placenta also does not express certain steroidogenic enzymes and, as mentioned previously, is an incomplete endocrine organ. It lacks the enzymes required to form cholesterol, as well as those required to convert progesterone to androgens, and subsequently estrogens.