1. Production of male pseudohermaphroditism in rats by two new inhibitors of steroid 17alpha-hydroxylase and C 17-20 lyase.
- Author
-
Goldman AS, Eavey RD, and Baker MK
- Subjects
- Androstadienes pharmacology, Animals, Animals, Newborn, Fetus drug effects, Hypospadias chemically induced, Ketosteroids pharmacology, Ketosteroids toxicity, Male, Organ Size drug effects, Pregnanediones pharmacology, Rats, Steroids, Brominated pharmacology, Steroids, Brominated toxicity, Testis drug effects, Testis embryology, Testis enzymology, Urea pharmacology, Androstadienes toxicity, Disorders of Sex Development chemically induced, Lyases antagonists & inhibitors, Pregnanediones toxicity, Steroid Hydroxylases antagonists & inhibitors
- Abstract
Two new synthetic steroid analogues, (I) 16beta-bromo-3beta,17alpha-dihydroxy-5alpha-pregnane-11,20-dione and (II) 17beta-ureido-1,4-androstadien-3-one have been shown to give kinetic patterns consistent with active-site-directed irreversible inhibition of adult rat testicular microsomal steroid 17alpha-hydroxylase and C17-20 lyase in vitro. Administration of both analogues to adult male rats for 24 h produced potent inhibition of these testicular enzymes in vivo. Given to pregnant rats during the critical period of male organogenesis they produced hypospadias: a characteristic of the syndrome in man in which these enzymes are defective genetically. Given to male rat pups during the first 9 days of life, inhibitor II produced significantly smaller prostates and seminal vesicles in adulthood, indicating the usefulness of this inhibitor in studies on the role of testosterone in neonatal programming of target organ size in adulthood. Thus, two new enzyme inhibitors have been shown to block testosterone production in the foetal and neonatal rat selectively at the site of the hydroxylase without other apparent hormonal effects or influence on adrenal size.
- Published
- 1976
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