TY - JOUR
T1 - Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol
AU - Nakamura, Daichi
AU - Yanagiba, Yukie
AU - Duan, Zhiwen
AU - Ito, Yuki
AU - Okamura, Ai
AU - Asaeda, Nobuyuki
AU - Tagawa, Yoshiaki
AU - Li, Chun Mei
AU - Taya, Kazuyoshi
AU - Zhang, Shu Yun
AU - Naito, Hisao
AU - Ramdhan, Doni Hikmat
AU - Kamijima, Michihiro
AU - Nakajima, Tamie
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Scientific Research ( B. 14370121 and 17310033 ) from the Japan Society for the Promotion of Science (JSPS) .
PY - 2010
Y1 - 2010
N2 - Bisphenol A (BPA) causes reproductive toxicities, but the mechanisms are still unclear. In the present study, we sought to clarify these mechanisms in comparison with those of 17β-estradiol (E2). Prepubertal Wistar/ST male rats (4 weeks old) were subcutaneously administered BPA (0, 20, 100 and 200mg/kg/day) or E2 (10 and 100μg/kg/day) for 6 weeks. Both BPA and E2 treatments decreased plasma and testicular testosterone levels, and plasma luteinizing hormone (LH), but not E2 and follicle-stimulating hormone levels, though E2 treatment increased its plasma level. In relation to the decreased testosterone levels, BPA and E2 decreased expressions of steroidogenic enzymes and cholesterol carrier protein in Leydig cells. Thus, decreased testosterone levels in plasma might have resulted from decreased expressions of these enzymes and protein as well as from decreased plasma LH levels. Interestingly, the changes in steroidogenic enzymes and carrier protein were observed at lower levels of exposure to BPA or E2 than those inhibiting plasma LH levels. Microscopically, 200mg/kg BPA and 100μg/kg E2 significantly decreased Leydig cell numbers in the testis. In addition, BPA and E2 also decreased expression of estrogen receptor α-mRNA, which might be related to the decreased numbers of Leydig cells. Thus, BPA directly affects not only the Leydig cells but also the pituitary gland, but the former may be impaired at lower exposure concentrations than the latter.
AB - Bisphenol A (BPA) causes reproductive toxicities, but the mechanisms are still unclear. In the present study, we sought to clarify these mechanisms in comparison with those of 17β-estradiol (E2). Prepubertal Wistar/ST male rats (4 weeks old) were subcutaneously administered BPA (0, 20, 100 and 200mg/kg/day) or E2 (10 and 100μg/kg/day) for 6 weeks. Both BPA and E2 treatments decreased plasma and testicular testosterone levels, and plasma luteinizing hormone (LH), but not E2 and follicle-stimulating hormone levels, though E2 treatment increased its plasma level. In relation to the decreased testosterone levels, BPA and E2 decreased expressions of steroidogenic enzymes and cholesterol carrier protein in Leydig cells. Thus, decreased testosterone levels in plasma might have resulted from decreased expressions of these enzymes and protein as well as from decreased plasma LH levels. Interestingly, the changes in steroidogenic enzymes and carrier protein were observed at lower levels of exposure to BPA or E2 than those inhibiting plasma LH levels. Microscopically, 200mg/kg BPA and 100μg/kg E2 significantly decreased Leydig cell numbers in the testis. In addition, BPA and E2 also decreased expression of estrogen receptor α-mRNA, which might be related to the decreased numbers of Leydig cells. Thus, BPA directly affects not only the Leydig cells but also the pituitary gland, but the former may be impaired at lower exposure concentrations than the latter.
UR - http://www.scopus.com/inward/record.url?scp=77950476594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77950476594&partnerID=8YFLogxK
U2 - 10.1016/j.toxlet.2010.02.002
DO - 10.1016/j.toxlet.2010.02.002
M3 - Article
C2 - 20144698
AN - SCOPUS:77950476594
SN - 0378-4274
VL - 194
SP - 16
EP - 25
JO - Toxicology Letters
JF - Toxicology Letters
IS - 1-2
ER -