The structures of the six principal steroid hormones (actually seven structures, including the two forms of aldosterone) enzymatically produced by the adrenal cortex, and three related drug forms, dexamethasone, prednisolone, and RU-486 (mifepristone), are shown in Figure 1. Each background color (green, peach, and light blue) defines the appropriate zona layer.

Fig1. Presentation of the chemical structure of seven key biosynthesized steroids and three chemically synthesized steroid drugs. The chemical structure of the key steroids produced by each zona of the adrenal cortex is as follows. The outermost zona glomerulosa produces aldosterone (green background). The biological properties of aldosterone are discussed in Chapter 15. The second layer, the zona fasciculata, produces cortisol and corticosterone (pink background). The innermost zona reticularis is the source of two androgens, namely dehydroepiandrosterone (DHEA) and testosterone (blue background). Also shown are the chemical structures of three steroid drugs, namely dexamethasone, prednisolone, and mifepristone (RU-486). Dexamethasone has both immunosuppressant and anti-inflammatory effects. It is ~20× more potent than cortisol and is devoid of aldosterone effects. RU-486 is used to block pregnancies.

The chemical structure and biological relationships of the naturally occurring glucocorticoids (cortisol and corticosterone) and the drug form, dexamethasone, are members of the ~100 steroid hormones .

The naturally occurring cortisol is the most prevalent member of the family of glucocorticoids and binds tightly to the glucocorticoid nuclear receptor. Whenever the blood concentration of cortisol falls below the normal circulating concentration of 6–20 μg/100 mL, additional cortisol will be produced. The daily secretory rate of cortisol is 10–20 mg/day. Additional cortisol will be secreted in response to a low blood concentration of cortisol; see Table 1. Also, when an individual experiences significant levels of stress, there will be an increased production of cortisol.

Table1. Normal Values for Steroids from the Adrenal Cortex

Cortisol’s most important action is to increase and maintain blood glucose levels via the biochemical process of gluconeogenesis in the combined actions of muscle cells, fat cells, and liver cells; see Figure 2. Cortisol, acting through its nuclear receptor in muscle cells inhibits protein synthesis and stimulates proteolysis, which produces free amino acids that will be transmitted via the circulatory system to liver cells and converted to glucose and then stored as glycogen. Similarly, cortisol and its nuclear receptor in fat cells inhibits lipogenesis (conversion of glucose carbons to fatty acids and stored as triglycerides), but stimulates lipolysis (breakdown of triglycerides to fatty acids). The fatty acids will subsequently be transferred through the circulatory system to liver cells, converted to glucose and stored as glycogen.

Fig2. Cell-specific actions of cortisol on muscle, liver, and fat cells. Cortisol in muscle cells inhibits protein synthesis and in fat cells inhibits lipogenesis. Cortisol, acting through its nuclear receptor in muscle cells, inhibits protein synthesis and stimulates proteolysis which produces free amino acids that will be transmitted via the circulatory system to liver cells and converted to glycogen. Similarly, cortisol and its receptor in fat cells inhibits lipogenesis which is the process of acquiring blood glucose and storing it as fat. Cortisol also stimulates lipolysis, the breakdown of the triglycerides to free fatty acids and glycerol. The fatty acids will subsequently be transferred through the circulatory system to liver cells and stored as glycogen. Both the fatty acids and the amino acids will subsequently be transferred through the circulatory system to liver cells and stored as glycogen.

Special suggestion for the reader: Chapter 2 is the foundation from a steroid hormone perspective for Chapters 10 (cortisol), 12 (androgens), 13 (estro gens+progesterone), 14 (pregnancy and lactation), and 15 (aldosterone). Chapter 2 covers only chemistry, bio synthesis, and metabolism of all biologically produced steroids. This chapter focuses mainly on the anatomical complexity of the adrenal gland and its three zonas as well as the production by the zona fasciculata of cortisol and corticosterone. Those readers who wish further information on androgens, estrogens, progestins, and mineralocorticoids should visit Chapter 2.

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