Part of “CHAPTER 72 – SYNTHESIS AND METABOLISM OF CORTICOSTEROIDS“

The liver and the kidney are the principal organs involved in clearing the steroid hormones from the circulation. Although most tissues can metabolize steroids, the liver is the primary site of steroid hormone metabolism, and the kidney is the primary site of steroid hormone excretion. Unconjugated steroids that are filtered by the kidney are largely reabsorbed. Hepatic metabolism accomplishes two functions: a decrease in the biologic activity of the hormones; and an increase in their water solubility, because of conversion to a hydrophilic form that can be excreted in urine. Additional metabolism and excretion may take place in the gut, although most of the metabolized products are reabsorbed.

Because plasma cortisol is bound with such high affinity, it is relatively protected from degradation. The plasma t_1/2 of cortisol is 60 to 100 minutes. This contrasts with many other steroids, such as aldosterone, DHEA, androstenedione, testosterone, and estradiol, that have metabolic clearance rates of ˜2000 L per day, corresponding to a t_1/2 of under 20 minutes. Although these compounds also circulate in a bound form, they dissociate more rapidly from their binding proteins, making them more susceptible to degradation. The episodic secretion of these adrenal hormones, combined with this short t_1/2, results in wide fluctuations in plasma steroid concentrations. By contrast, the steroid sulfates, such as DHEAS, which bind with high affinity to albumin, are cleared slowly from the circulation and have high stable plasma concentrations.

The pathways involved in metabolism of the steroids yield more than 50 different metabolic products formed by approximately a dozen distinct enzymatic reactions.