Effects of Age and Sex on3H-Cortisol Uptake, Binding and Metabolism in Liver and on Enzyme Induction Capacity

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Abstract
The effects of age and sex upon the uptake, metabolism and binding of 3H-cortisol by rat liver and on the induction of hepatic tyrosine aminotransferase were studied. The livers of fetal rats, one day before term, concentrate the hormone only 20% as well as adult livers. Fetal hepatic cytosol proteins bind only 9% as much of the injected hormone as do those from adult female rats. Hormone uptake and binding reach nearly adult levels in 24-hr-old rats. The major binding proteins are named I, II and III in the order of increasing affinity for DEAE Sephadex A-50. After fractionation of adult cytosol proteins, 3–5, 4–10 and 80–90% of the recovered cortisol radioactivity associates with Binders I, II and III, respectively. The amount of radioactivity in Binder I is constant regardless of age. However, the relative amounts of radioactivity associated with Binders II (68–73%) and III (22–28%) in fetal cytosols are reversed from the adult pattern. After 16 days, the radioactivity in Binder II begins to fall and the radioactivity in Binder III begins to rise. At 39 days, a pattern of bound radioactivity resembling that of the adult is seen. Up to 11 days after birth, hepatic tyrosine aminotransferase levels are not affected by cortisol administration. At days 15, 26 and 39, injection of cortisol (100 mg/ kg body wt) results in 2.2-, 3.1- and 5.2-fold increases in the hepatic enzyme levels. The increase in the inducibility of hepatic tyrosine aminotransferase parallels the shift in the hepatic cortisol metabolite binding from the fetal to the adult pattern. Adult male rats metabolize cortisol to produce a small amount of a non-anionic compound (A) and larger amounts of 3 anionic derivatives B, C and D (in order of increasing negative charge). Adult female liver forms only C. Fetal rats do not produce these metabolites to any great extent. Over 90% of the radioactivity from fetal liver is comprised of cortisol and tetrahydrocortisol. Within 4 days after birth, rats start to produce metabolite C. Metabolites B and D appear only in male rats 32 days of age or older. (Endocrinology88: 1448, 1971)

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