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Pubertal administration of DEHP delays puberty, suppresses testosterone production and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans Rats
NORIEGA, N., K. HOWDESHELL, J. R. FURR, C. R. LAMBRIGHT, V. S. WILSON, AND L. E. GRAY. Pubertal administration of DEHP delays puberty, suppresses testosterone production and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans Rats. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 111(1):163-178, (2009).
A low to high dose study on the effects of DEHP in male rat puberty and steroid hormone production
While 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 DEHP accelerate puberty by enhancing testicular androgen synthesis. The current study was designed to determine if the dose response to DEHP was non-monotonic, 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/d. These effects were generally of greater magnitude in LE than SD rats. By contrast, alterations in testis histopathology (300 and 900 mg/kg/d) 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 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 hCG 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/d in either LE or SD rats, as some have hypothesized. Taken together, these results do not provide any evidence of a non-monotonic dose response to DEHP during puberty.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
REPRODUCTIVE TOXICOLOGY DIVISION