Androgenic deficiency in male rats treated with perfluorodecanoic acid.
Effects of perfluorodecanoic acid (PFDA, 20-80 mg/kg, ip) on the androgenic status of sexually mature male rats were investigated 7 days after treatment. PFDA decreased plasma androgen concentrations in a dose-dependent fashion with an ED50 of approximately 30 mg/kg. The highest dose of PFDA decreased plasma testosterone and 5 alpha-dihydrotestosterone concentrations to 12 and 18%, respectively, of ad libitum-fed control (ALC) values. Secondary to the decreased plasma androgen concentrations were dose-related decreases in the weights and epithelial heights of accessory sex organs. Results from pair-fed control (PFC) rats show that hypophagia in PFDA-treated rats was not a major cause of the low plasma androgen concentrations. When rats were castrated and implanted with testosterone-containing capsules, PFDA-treated and ALC rats had similar plasma testosterone concentrations and secondary sex organ weights. Therefore, the androgenic deficiency in intact PFDA-treated rats does not result from increased plasma clearance of androgens. Rather, PFDA must cause the androgenic deficiency by decreasing the secretion of testosterone from the testis. The decrease in testosterone secretion does not appear to result from a decrease in plasma luteinizing hormone (LH) concentrations, because plasma LH concentrations were not significantly altered by PFDA treatment. This finding suggests that PFDA treatment decreases testicular responsiveness to LH stimulation. The observation that PFDA treatment reduced the secretion of testosterone by testes stimulated in vitro with the LH analog human chorionic gonadotropin demonstrates that this is the case. In addition, since plasma LH concentrations did not increase in response to the low plasma androgen concentrations in PFDA-treated rats, we suggest that PFDA disrupts the normal feedback relationship which exists between plasma androgen and LH concentrations.
Bookstaff
R C
RC
School of Pharmacy, University of Wisconsin, Madison 53706.
Moore
R W
RW
Ingall
G B
GB
Peterson
R E
RE
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003652:Decanoic Acids / Q000633:toxicity*; D013196:Dihydrotestosterone / Q000097:blood*; D002149:Energy Intake / Q000187:drug effects; D005246:Feedback / Q000187:drug effects; D005466:Fluorocarbons / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000097:blood / Q000502:physiology; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D013739:Testosterone / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology
D003652:Decanoic Acids; D005466:Fluorocarbons; D013196:Dihydrotestosterone; C036567:perfluorodecanoic acid; D013739:Testosterone; D007986:Luteinizing Hormone