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Effects of drugs and environmental chemicals on steroid metabolism
Author(s) -
Conney A.H.,
Levin W.,
Jacobson M.,
Kuntzman R.
Publication year - 1973
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1973144part2727
Subject(s) - chemistry , estrone , phenobarbital , steroid , hydroxylation , microsome , metabolism , pharmacology , drug metabolism , medicine , endocrinology , testosterone (patch) , hormone , enzyme , biochemistry , biology
Drugs and steroids are hydroxylated by a common enzyme system in rat liver microsomes. In accord with this concept, treatment of rats with drugs or environmental chemicals that stimulate or inhibit hepatic drug metabolism can alter the hydroxylation of steroid hormones. Examples of compounds that stimulate the microsomal hydroxylation of drugs and steroids include phenobarbital, phenylbutazone, DDT, and chlordane; inhibitors of microsomal hydroxylation include SKF 525–A, chlorthion, carbon tetrachloride, ami carbon monoxide. Treatment of rats or guinea pigs with phenobarbital induces the synthesis of liver microsomal enzymes that hydroxylate progesterone, estradiol, estrone, deoxycorticosterone, testosterone, Δ 4 ‐androstene‐3,17‐dione and cortisol, whereas treatment of rats with SKF 525‐A or carbon tetrachloride inhibits the activity of microsomal enzymes that hydroxylate steroids. The stimulatory or inhibitory effect of drugs on the enzymatic metabolism of steroids is reflected in vivo by an altered metabolism and action of steroids. Accordingly, pretreatment of rats with phenobarbital decreases the uterotropic action of estradiol and estrone, the growth‐promoting effect of testosterone on the seminal vesicles, and the anesthetic action of progesterone and deoxycorticosterone. Pretreatment of rats with SKF 525‐A or carbon tetrachloride enhances the uterotropic action of estrone. Drugs that stimulate steroid hydroxylation in animals also influence steroid metabolism in man. Phenobarbital, N‐phenylbarbital, diphenylhydantoin, phenylbutazone, o,p'‐DDD and DDT are potent stimulators of microsomal hydroxylation in animals, and these compounds stimulate the urinary excretion of 6β‐hydroxycortisol in man. In addition, treatment of humans with phenobarbital alters the proportion of testosterone metabolites excreted in the urine and decreases the action of prednisone in steriod‐dependent asthmatics. Since the human fetus, placenta, and mother hydroxylate steroids in many positions, the influence of drugs or environmental chemicals on these metabolic pathways should be studied during pregnancy.