Toxicology Letters

Volume 194, Issues 12, 15 April 2010, Pages 1625

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

Daichi Nakamuraa, Yukie Yanagibaa, Zhiwen Duana, Yuki Itoa, 1, Ai Okamuraa, Nobuyuki
Asaedab,

Yoshiaki Tagawab, ChunMei Lic, d, Kazuyoshi Tayac, d, Shu-Yun Zhanga, 2, Hisao Naitoa,

Doni Hikmat Ramdhana, Michihiro Kamijimaa, 1, Tamie Nakajimaa, ,

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 17-estradiol (E2).
Prepubertal Wistar/ST male rats (4 weeks old) were subcutaneously administered BPA (0, 20, 100
and 200 mg/kg/day) or E2 (10 and 100 g/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,
200 mg/kg BPA and 100 g/kg E2 significantly decreased Leydig cell numbers in the testis. In
addition, BPA and E2 also decreased expression of estrogen receptor -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.

Keywords

Bisphenol A; 17-Estradiol; Leydig cells; Reproductive toxicity; Steroidogenesis

Corresponding author. Tel.: +81 52 744 2122; fax: +81 52 744 2126.

1Current address: Department of Occupational and Environmental Health, Nagoya City University
Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

2Current address: Laboratory of Pharmacology, National Institute of Environmental Health Sciences,

National Institutes of Health, Research Triangle Park, NC 27709, USA.

Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Oral exposure to low-dose bisphenol A aggravates testosterone-induced benign hyperplasia
prostate in rats

1. Jian-Hui Wu wwjh_731@yahoo.com.cn

1. Fudan University and Shanghai Institute of Planned Parenthood Research, Shanghai,

China

1. Xiu-Rong Jiang

1. National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Shanghai
Institute of Planned Parenthood Research, Shanghai, China

1. Gui-Ming Liu

1. National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Shanghai
Institute of Planned Parenthood Research, Shanghai, China

1. Xiang-Yun Liu

1. National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Shanghai
Institute of Planned Parenthood Research, Shanghai, China

1. Gui-Lin He

1. National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Shanghai
Institute of Planned Parenthood Research, Shanghai, China

1. Zu-Yue Sun

1. National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Shanghai
Institute of Planned Parenthood Research, Shanghai, China

Abstract

The declining level of androgen during aging, associated with an inclining level of estrogen, has been
hypothesized to be important in the development of benign prostatic hyperplasia (BPH). Within
physiologic range, increasing estrogen levels can stimulate prostate to develop and permanently
increase prostate size. As an estrogenic endocrine disruptor, bisphenol A (BPA) might be stimulatory
to prostate development. We further hypothesized that low dose BPA could induce hyperplasia
prostate to proliferate and aggravate the symptom of BPH in male SD rats. BPH was induced by
testosterone and then treated with BPA (10, 30, or 90 g/kg, i.g., daily), 17-estradiol (E 2; 50.0 g/kg,
s.c., daily), or vehicle for 4 weeks. We found that weight and volume in rats treated with low dose
BPA (10 g/kg) was higher than that of model control, and BPA significantly increased the relative
weight of prostate (p < 0.01). For prostate lobes, BPA 10 g/kg/day significantly increased relative
weight of ventral prostate (VP), weight and relative weight of dorsolateral prostate (DLP) (p < 0.05).
And histopathology results showed that height of epithelial cell (HEC) of VP and DLP in BPA group
were significantly higher than that of model control (p < 0.01). BPA could also decrease testostertone
level and increase prostate-specific antigen level. E 2 treatment also showed an obvious effect on
relative weight of VP and DLP, HEC, and hormone levels. We concluded that environment exposure to
low dose of BPA may induce prostate to proliferate and aggravate testosterone-induced benign
hyperplasia prostate in rats.