Effects of prenatal administration of mestranol and two progestins on testosterone synthesis and reproductive tract development in male rats.
The oestrogen mestranol (0, 0.01, 0.1 mg/kg body weight per day) and the progestins medroxyprogesterone-acetate and norethisterone (0, 2, 20 mg/kg body weight per day each) in sesame oil were intubated intragastrically daily during gestational days 14.5 through 19.5 to pregnant rats. Males were studied as 20.5-day-old foetuses and 4-month-old adults for serum testosterone and LH concentrations, in vitro testosterone synthesis, anogenital distance (foetuses only) and testes, seminal vesicle and ventral prostate weights. Administration of 0.1 mg mestranol decreased by 35 to 70% basal and LH-stimulated testosterone synthesis by both foetal and adult testes in vitro (P less than 0.01). Foetal body weights (P less than 0.05), but not anogenital distances, were significantly decreased. Testosterone content in adult sera was reduced significantly (P less than 0.05) to less than 50% of control. Testes, ventral prostate, seminal vesicle and epididymal weights were unaffected by treatment. Medroxyprogesterone acetate or norethisterone administration did not alter testes endocrine function in foetal or adult offspring. In a small number of rats, pregnant for 10.5, 14.5 or 18.5 days, [3H]ethinyloestradiol was intubated and foetal and placental tissue examined for appearance and content of radioactivity. Radioactivity was detected in 10.5, 14.5 and 18.5 days old placentas, and 14.5 and 18.5 days old foetal liver, gonads and external genitalia. With [3H]medroxyprogesterone acetate, radioactivity was localized in 14.5 day placenta and foetal tissues. Thin-layer chromatographic analysis showed most of the activity to migrate as authentic ethinyloestradiol or medroxyprogesterone acetate. These results demonstrate inhibition of testicular testosterone synthesis by mestranol, presumably by being transferred across the placenta and acting in the foetus.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D017258:Medroxyprogesterone Acetate; D008656:Mestranol / Q000008:administration & dosage*; D009640:Norethindrone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011467:Prostate / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000187:drug effects; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000096:biosynthesis* / Q000493:pharmacokinetics
D013739:Testosterone; D004997:Ethinyl Estradiol; D008656:Mestranol; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone; D009640:Norethindrone