Bisphenol A Modifies the Regulation Exerted by Testosterone on 5α-Reductase Isozymes in Ventral Prostate of Adult Rats

Abstract

The development, growth, and function of the prostate gland depend on androgen stimulation. The primary androgen in prostate is 5α-dihydrotestosterone (DHT) which is synthesized from circulating testosterone (T) through the action of 5α-reductase (5α-R). Although 5α-R occurs as five isozymes, only 5α-R1 and 5α-R2 are physiologically involved in steroidogenesis. The endocrine disruptor bisphenol A (BPA) alters sexual organs, including the prostate. Our previous findings indicated that BPA decreased the expression of 5α-R1 and 5α-R2 in rat prostate but also circulating T. Thus, it is unclear whether BPA exerts this effect on 5α-R isozymes by reducing circulating T or by any other mechanism. In this study, we examine the effects of short-term exposure to BPA at doses below 25 μg/Kg/d and above 300 μg/Kg/d of the TDI on mRNA levels of 5α-R1 and 5α-R2 in prostate of adult castrated rats supplemented with T to achieve constant circulating T levels. mRNA levels were measured by absolute quantitative RT-PCR, T levels by RIA, and DHT levels by ELISA. Our results indicated that in castrated rats treated with T BPA at the two doses studied significantly decreased the mRNA levels of both 5α-R isozymes in a dose-dependent manner without modifications in circulating T.

Low-dose effects of bisphenol A on early sexual development in male and female rats

“…One example of such a substance is the anti-androgenic drug and 5a-reductase inhibitor finasteride (Clark et al 1990, Bowman et al 2003, Christiansen et al 2009). Interestingly, a new study that examines the effects of short-term exposure to BPA on mRNA levels of 5a-reductase isozymes in prostate of adult castrated rats show that BPA significantly decreased the mRNA levels of both 5a-reductase isozymes (Sánchez et al 2013). This indicates that BPA is a 5a-reductase inhibitor and could be one explanation for the shallow dose-response similarly as for finasteride.…”

Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine–serotonin systems in the prefrontal cortex of juvenile female rats

“…These discrepancies may reflect temporal or compensatory effects as a result of differential exposure times, or dose-dependent mechanisms (Vandenberg et al, 2012). Another possibility is that BPA, due to its anti-androgenic activity through androgen receptor (AR) antagonism (Lee et al, 2003;Sánchez et al, 2013), might differentially regulate 5α-R1 and Fig. 2.…”

Effects of Bisphenols on Testicular Steroidogenesis

“…Treatment with increasing concentrations of BPA (1 to 1,000 nM) did not significantly lower basal or hCG-stimulated T secretion by primary culture of LCs of young adult male rats ( 42 ). However, although Sánchez et al reported that low-dose BPA did not decrease T levels in Wistar rats, dihydrotestosterone levels decreased ( 43 ). Gamez et al reported that exposure to low-dose BPA led to an increase in serum LH and FSH levels in young Wistar rats ( 44 ).…”