Pubertal administration of DEHP delays puberty, suppresses testosterone production, and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans rats.
Although is clear that exposure to high dosage levels of some phthalates delays the onset of puberty in the male rat, it has been hypothesized that low levels of di(2-ethylhexyl) phthalate (DEHP) accelerate puberty by enhancing testicular androgen synthesis. The current study was designed to determine if the dose response to DEHP was nonmonotonic, as hypothesized. Pubertal administration of DEHP delayed the onset of puberty and reduced androgen-dependent tissue weights in both Long-Evans (LE) and Sprague-Dawley (SD) male rats 300 and 900 mg DEHP/kg/day. These effects were generally of greater magnitude in LE than SD rats. By contrast, alterations in testis histopathology (300 and 900 mg/kg/day) were more severe in SD than in LE rats. Taken together, these results suggest that DEHP may be acting on the pubertal male rat testis via two modes of action; one via the Leydig cells and the other via the Sertoli cells. Treatment with DEHP generally reduced serum testosterone and increased serum luteinizing hormone (LH) levels, demonstrating that the reduction in testosterone was due to the effect of DEHP on the testis and not via an inhibition of LH from hypothalamic-pituitary axis. Testosterone production ex vivo (with and without human chorionic gonadotropin stimulation) was consistently reduced in males at the time of puberty and shortly thereafter. DEHP treatment did not accelerate the age at puberty or enhance testosterone levels at 10 or 100 mg/kg/day in either LE or SD rats, as some have hypothesized. Taken together, these results do not provide any evidence of a nonmonotonic dose response to DEHP during puberty.
Noriega
Nigel C
NC
Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA.
Howdeshell
Kembra L
KL
Furr
Jonathan
J
Lambright
Christy R
CR
Wilson
Vickie S
VS
Gray
L Earl
LE
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005837:Genitalia, Male / Q000187:drug effects / Q000254:growth & development*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000097:blood
D013739:Testosterone; D007986:Luteinizing Hormone; D004051:Diethylhexyl Phthalate