Foetal exposure to low doses of cyproterone acetate in the rat leads to functional endocrine abnormalities despite normal sexual morphogenesis.
Cyproterone acetate (CPA), an anti-androgen and a gestagen, was administered to pregnant Wistar rats at very low doses (0.5 or 1.0 mg/day) between days 15 and 20 of pregnancy. No anatomical abnormalities were observed in external genitalia of their offspring, either immediately after birth or upon reaching maturity. However, when these animals were studied in adulthood, several endocrine abnormalities became apparent. While the pituitary content of Prl decreased in the CPA-exposed offspring, the amount of LH increased. Plasma Prl was lower and FSH was higher in treated females whereas plasma LH was higher in both sexes compared to controls. Treatment induced a Prl-responsiveness to TRH in both sexes and an enhanced LH- and FSH-response to GnRH in females. Testicular weights, LH/hCG receptors in testicular membrane preparations and testosterone response to in vivo hCG stimulation were identical in both the treated and control groups. Basal testosterone, however, was increased in the face of decreased ventral prostate weight and of decreased androgen receptors in prostate cytosol, indicating androgen resistance of the target organ. Females displayed normal oestrous cycles, but possessed enlarged ovaries and uteri. The decrease in oestrogen receptors (ER) in uterine cytosol during oestrus and the relative increase of ER in dioestrus were consistent with enhanced oestrogenic action, presumably by increased oestrogen secretion by the hyperstimulated ovaries.
D000818:Animals; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017373:Cyproterone Acetate; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005836:Genitalia, Female / Q000187:drug effects*; D005837:Genitalia, Male / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects*; D011247:Pregnancy; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D011987:Receptors, Steroid / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D011956:Receptors, Cell Surface; D011987:Receptors, Steroid; D013739:Testosterone; D017373:Cyproterone Acetate; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003534:Cyproterone