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.

Highlights

  • The prostate plays a key role in the reproductive mechanism of a man

  • Of the five types of 5α-R enzymes characterized to date, only type 1 (5αR1) and type 2 (5α-R2) are believed to be physiologically involved in steroidogenesis [4]. 5α-R1 isozyme occurs in tissues such as the liver [5], the skin, and the brain, where it acts as a key enzyme in the biosynthesis of neuroactive steroids [6,7,8,9], it is expressed in the prostate [10, 11]. 5α-R2 isozyme is predominantly expressed in male reproductive tissues including the prostate [10,11,12,13]

  • All groups treated with T had a significant increase in 5α-R1 mRNA levels in comparison with castrated rats without T treatment (Figure 2(a)). Both groups treated with bisphenol A (BPA) at the doses of 25 μg/Kg/d and 300 μg/Kg/d had significant decreased 5α-R1 mRNA levels in comparison with castrated rats treated with T (Figure 2(a))

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Summary

Introduction

The prostate plays a key role in the reproductive mechanism of a man. The prostate is a secretory gland surrounding the urethra at the base of the bladder. As part of the male reproductive system, the prostate gland’s primary function is to secrete nutrients, ions, proteins, and hormones that are added to the ejaculatory fluid produced by the seminal vesicles. These molecules are necessary for the survival of the spermatozoids during their journey through the female reproductive tract. 5α-R1 isozyme occurs in tissues such as the liver [5], the skin, and the brain, where it acts as a key enzyme in the biosynthesis of neuroactive steroids [6,7,8,9], it is expressed in the prostate [10, 11]. Development, and function of the prostate are mainly regulated by 5α-R2, with 5α-R1 contributing to these events [10, 14, 15]

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