The high incidence of prostate cancer (PCa) and benign prostatic hypertrophy (BPH) in elderly men is a cause of increasing public health concern. In recent years, various environmental endocrine disruptors, such as bisphenol A (BPA), have been shown to disrupt sexual organs, including the prostate gland. However, the mechanisms underlying these effects remain unclear. Because androgens and estrogens are important factors in prostate physiopathology, our objective was to examine in rat ventral prostate the effects of adult exposure to BPA on 5α-Reductase isozymes (5α-R types 1, 2, and 3) and aromatase, key enzymes in the biosynthesis of dihydrotestosterone and estradiol, respectively. Adult rats were subcutaneously injected for four days with BPA (25, 50, 300, or 600 µg/Kg/d) dissolved in vehicle. Quantitative RT-PCR, western blot and immunohistochemical analyses showed lower mRNA and protein levels of 5α-R1 and 5α-R2 in BPA-treated groups versus controls but higher mRNA levels of 5α-R3, recently proposed as a biomarker of malignancy. However, BPA treatment augmented mRNA and protein levels of aromatase, whose increase has been described in prostate diseases. BPA-treated rats also evidenced a higher plasma estradiol/testosterone ratio, which is associated with prostate disease. Our results may offer new insights into the role of BPA in the development of prostate disease and may be of great value for studying the prostate disease risk associated with exposure to BPA in adulthood.

The enzyme 5α‐reductase (5α‐R) is present in many mammalian tissues, including the brain. The physiological importance of 5α‐R in the brain derives from its capability to convert testosterone (T) to a more potent androgen, dihydrotestosterone (DHT), and to convert progesterone and deoxycorticosterone (DOC) to their respective 5α‐reduced derivatives, precursors of allopregnanolone and tetrahydroDOC, potent allosteric modulators of the γ‐aminobutyric acid receptor (GABA _A ‐R). 5α‐R occurs as two isoforms, 5α‐R type 1 (5α‐R1) and 5α‐R type 2 (5α‐R2). We studied the effects of T and DHT on the mRNA levels of both 5α‐R isozymes in the prefrontal cortex of the adult rat, using an accurate and precise method that combines the high specificity of one‐step quantitative RT‐PCR with the sensitivity of capillary electrophoresis. Our results demonstrate that both isozymes of 5α‐R are expressed in the cerebral cortex of adult rats. The gene expression of 5α‐R type 2 is under the positive control of T and DHT. The gene that codes for 5α‐R type 1 is not constitutive, because its expression is negatively regulated by T and DHT. These results open up a new research line that may lead to a better understanding of the role of 5α‐R isozymes in the physiology of the central nervous system.—Torres, J. M., Ortega, E. Differential regulation of steroid 5α‐reductase isozymes expression by androgens in the adult rat brain. FASEB J. 17, 1428–1433 (2003)