Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol

Daichi Nakamura, Yukie Yanagiba, Zhiwen Duan, Yuki Ito, Ai Okamura, Nobuyuki Asaeda, Yoshiaki Tagawa, Chun Mei Li, Kazuyoshi Taya, Shu Yun Zhang, Hisao Naito, Doni Hikmat Ramdhan, Michihiro Kamijima, Tamie Nakajima

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)16-25
Number of pages10
JournalToxicology Letters
Volume194
Issue number1-2
DOIs
Publication statusPublished - 02-03-2010

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Testosterone
Testis
Estradiol
Leydig Cells
Plasmas
Luteinizing Hormone
Carrier Proteins
Enzymes
bisphenol A
Follicle Stimulating Hormone
Pituitary Gland
Estrogen Receptors
Toxicity
Rats
Cell Count
Cholesterol
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Nakamura, Daichi ; Yanagiba, Yukie ; Duan, Zhiwen ; Ito, Yuki ; Okamura, Ai ; Asaeda, Nobuyuki ; Tagawa, Yoshiaki ; Li, Chun Mei ; Taya, Kazuyoshi ; Zhang, Shu Yun ; Naito, Hisao ; Ramdhan, Doni Hikmat ; Kamijima, Michihiro ; Nakajima, Tamie. / Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol. In: Toxicology Letters. 2010 ; Vol. 194, No. 1-2. pp. 16-25.
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abstract = "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.",
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Nakamura, D, Yanagiba, Y, Duan, Z, Ito, Y, Okamura, A, Asaeda, N, Tagawa, Y, Li, CM, Taya, K, Zhang, SY, Naito, H, Ramdhan, DH, Kamijima, M & Nakajima, T 2010, 'Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol', Toxicology Letters, vol. 194, no. 1-2, pp. 16-25. https://doi.org/10.1016/j.toxlet.2010.02.002

Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol. / Nakamura, Daichi; Yanagiba, Yukie; Duan, Zhiwen; Ito, Yuki; Okamura, Ai; Asaeda, Nobuyuki; Tagawa, Yoshiaki; Li, Chun Mei; Taya, Kazuyoshi; Zhang, Shu Yun; Naito, Hisao; Ramdhan, Doni Hikmat; Kamijima, Michihiro; Nakajima, Tamie.

In: Toxicology Letters, Vol. 194, No. 1-2, 02.03.2010, p. 16-25.

Research output: Contribution to journalArticle

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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

PY - 2010/3/2

Y1 - 2010/3/2

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.

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