Effects of an environmental anti-androgen on erectile function in an animal penile erection model.
OBJECTIVE
Erectile function is testosterone dependent. For example, interference with either the levels or receptor binding of this steroid hormone may induce erectile dysfunction. Several environmental contaminants can interfere with the actions of endogenous hormones and have been termed 'endocrine disrupters.' p,p-DDE, a prominent and persistent metabolite of the insecticide DDT, has been shown to be an androgen receptor antagonist. The objective was to determine whether endocrine disrupters, as exemplified by p,p-DDE, are factors in the etiology of erectile dysfunction.


METHODS
Using the established rat model of apomorphine-induced (80 microg./kg, s.c.) erections we assessed the dose-response effects of p,p-DDE in comparison to the known androgen receptor antagonist flutamide in acute (0.5 to 12 hours) and short-term (up to 8 weeks) experiments in both intact (Study 1) and castrated (Study 2) rats. As a follow up (Study 3), castrated rats treated with p,p-DDE were given increasing doses of testosterone (0.48 to 2.4 mg./kg., i.p.), eight weeks after p,p-DDE administration, to assess reversibility of p,p-DDE effect.


RESULTS
A single dose of flutamide (50 mg./kg., i.p.) was found to significantly decrease apomorphine-induced erections to less than 50% over 12 hours following flutamide administration with recovery of erectile response within 48 hours. In comparison, a single dose of p,p-DDE (500 mg./kg., i.p.) decreased apomorphine-induced erections for at least two weeks (1.15+/-0.3 versus 2.5+/-1.1). Castration significantly decreased apomorphine-induced erections to approximately 0.5 erections/30 minutes. Flutamide (50 mg./kg.; i.p.) or p,p-DDE (50 mg./kg.; i.p.) did not further suppress the apomorphine erections in castrated rats. Testosterone supplementation (480 microg./kg; s.c.) in vehicle treated castrated rats recovered erectile response to pre-castrated levels, whereas p,p-DDE treated castrated rats required 4 times the dose of testosterone (2 mg./kg.; s.c.) given to vehicle treated rats to recover erections.


CONCLUSIONS
The endocrine disrupter p,p-DDE can markedly interfere with erectile function and demonstrates persistence after a single dose. This supports our novel concept that environmental hormones may cause erectile dysfunction.
Brien
S E
SE
Department of Pharmacology & Toxicology, Queen's University, Kingston General Hospital, Ontario, Canada.
Heaton
J P
JP
Racz
W J
WJ
Adams
M A
MA
D000726:Androgen Antagonists / Q000009:adverse effects*; D000818:Animals; D002369:Castration; D003633:Dichlorodiphenyl Dichloroethylene / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000009:adverse effects*; D007172:Erectile Dysfunction / Q000139:chemically induced*; D005485:Flutamide / Q000009:adverse effects*; D007306:Insecticides / Q000009:adverse effects*; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology; D013997:Time Factors
D000726:Androgen Antagonists; D004785:Environmental Pollutants; D007306:Insecticides; D013739:Testosterone; D003633:Dichlorodiphenyl Dichloroethylene; D005485:Flutamide