Endocrine disrupting effect of di-(2-ethylhexyl)phthalate on female rats and proteome analyses of their pituitaries.
Di-(2-ethylhexyl)phthalate (DEHP) is a plasticizer and a ubiquitous environmental contaminant that may have adverse effects on human reproductive health. We examined the long-term exposure effects of DEHP on female rats and observed a strong effect on estrous cyclicity that produced a continuous diestrous stage. We found that the serum estradiol, follicle-stimulating hormone (FSH), pituitary FSH and luteinizing hormone levels were significantly reduced in the treated rats. To examine on the endocrine disrupting effects, we performed proteome-based analyses of their pituitaries, and found two proteins with remarkably reduced their levels. They were identified as the valosin-containing peptide/p97 (VCP/p97) and UMP-CMP kinase and their average protein spot intensities on statistical analysis of the spots differences of the treated/control rats were 0.13 and 0.21, respectively. Furthermore, there were 14 other proteins that had significantly changed levels, and their average protein spot intensities were in a range of 0.26 to 0.50 in 13 proteins and 2.74 in one. The reduction of in level of 7 proteins seems to be related to the intracellular protein transporting pathway, and it appears to suggest a slow down of gonadotrophin-releasing capability. Reduction of gonadotrophin release in the pituitary seems to lead to a decrease of serum estradiol level and continuous diestrous stage in estrous cyclicity.
Hirosawa
Narumi
N
Department of Biomedical Research Center, Division of Analytical Science, Saitama Medical School, Saitama, Japan.
Yano
Kazuyuki
K
Suzuki
Yuko
Y
Sakamoto
Yasushi
Y
D000818:Animals; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D004958:Estradiol / Q000097:blood; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D006062:Gonadotropins / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism*; D010968:Plasticizers / Q000494:pharmacology*; D020543:Proteome; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D006062:Gonadotropins; D010968:Plasticizers; D020543:Proteome; D004958:Estradiol; D004051:Diethylhexyl Phthalate