Prospective study on the sexual development of male and female 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 offspring's reproductive development. 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. Except for the highest dose of cimetidine (4.0 mg/ml drinking water) the drug had no effect on the dams' food and water consumption or body weight gain. In general, feminine sexual development as measured by pubertal onset, reproductive organ weights and adult estrous cyclicity, was unaffected by perinatal exposure to cimetidine. Similarly, early exposure to the drug had little effect on masculine sexual development. The developmental profile of serum dehydroepiandrosterone, androstenedione, testosterone and 5 alpha-dihydrotestosterone when measured at 1, 4 and 18 weeks of age, was unaffected by perinatal exposure to cimetidine. Furthermore, serum androgen concentrations and seminal vesicle weights following orchiectomy and androgen replacement were the same in control and cimetidine-exposed rats. In contrast, pituitary weights of adult males exposed to maternally administered cimetidine appeared to be insensitive to androgen regulation. However, taken in totality, our results do not support the concept that cimetidine is a reproductive teratogen.
Shapiro
B H
BH
Laboratories of Biochemistry, University of Pennsylvania School of Veterinary Medicine, Philadelphia.
Hirst
S A
SA
Babalola
G O
GO
Bitar
M S
MS
D000728:Androgens / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002927:Cimetidine / Q000633:toxicity*; D004971:Estrus / Q000187:drug effects; D005260:Female; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010500:Perinatology; D010902:Pituitary Gland / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D051381:Rats; D011919:Rats, Inbred Strains; D012741:Sexual Maturation / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
D000728:Androgens; D013739:Testosterone; D002927:Cimetidine