Developmental levels and androgen responsiveness of hepatic mono-oxygenases of male rats perinatally exposed to maternally administered cimetidine.
Cimetidine, a widely prescribed, potent histamine H2-receptor antagonist, is unrelatedly a mild antiandrogen. Since perinatal androgens are essential for normal masculine imprinting, we wanted to determine if maternally administered cimetidine interfered with the development of the male offspring's sex-dependent, hepatic drug-metabolizing enzymes. Cimetidine was administered in the mothers' drinking water at several levels reflecting both human and rat therapeutic-like doses from day 17 of gestation through day 7 of lactation. With the exception of a 30% decline in the Vmax for hexobarbital hydroxylase during adulthood, the developmental profile of microsomal drug-metabolizing enzymes, when measured at 1, 4 and 18 weeks of age, was generally unaffected by perinatal exposure to cimetidine. Furthermore, the levels of various components of the hepatic mono-oxygenase system (i.e. heme, cytochromes P-450 and b5, hexobarbital hydroxylase and p-chloro-N-methylaniline demethylase) following orchidectomy and androgen replacement at physiologic and inductive concentrations, were basically the same in control and cimetidine-exposed rats.
Shapiro
B H
BH
Laboratory of Biochemistry, University of Pennsylvania, School of Veterinary Medicine, Philadelphia 19104-6048.
Bitar
M S
MS
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D002927:Cimetidine / Q000633:toxicity*; D005260:Female; D007700:Kinetics; D008297:Male; D008431:Maternal-Fetal Exchange; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009919:Orchiectomy; D010105:Oxygenases / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens / Q000633:toxicity*; D013739:Testosterone / Q000378:metabolism
D013723:Teratogens; D013739:Testosterone; D002927:Cimetidine; D006899:Mixed Function Oxygenases; D010105:Oxygenases; C021352:hexobarbital hydroxylase; D000633:Aminopyrine N-Demethylase