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Bisphenol A modifies the regulation exerted by testosterone on 5 ? -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 5?-dihydrotestosterone (DHT) which is synthesized from circulating testosterone (T) through the action of 5?-reductase (5?-R). Although 5?-R occurs as five isozymes, only 5?-R1 and 5?-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 5?-R1 and 5?-R2 in rat prostate but also circulating T. Thus, it is unclear whether BPA exerts this effect on 5?-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 ?g/Kg/d and above 300 ?g/Kg/d of the TDI on mRNA levels of 5?-R1 and 5?-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 5?-R isozymes in a dose-dependent manner without modifications in circulating T.

SUBMITTER: Sanchez P

PROVIDER: S-EPMC3741927 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Bisphenol A modifies the regulation exerted by testosterone on 5 α -reductase isozymes in ventral prostate of adult rats.

Sánchez Pilar P Castro Beatriz B Torres Jesús M JM Olmo Asunción A del Moral Raimundo G RG Ortega Esperanza E

BioMed research international 20130725

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 decreas ...[more]

PMID: 23984391

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Project description:2-Difluoromethylornithine totally prevented any increases in putrescine and spermidine concentrations in the ventral prostate of castrated rats during a 6-day testosterone treatment. Prostatic ornithine decarboxylase activity was inhibited by 80%, whereas S-adenosylmethionine decarboxylase was stimulated by more than 9-fold. In seminal vesicle, the inhibition of putrescine and spermidine accumulation, as well as of ornithine decarboxylase activity, was only minimal, and no stimulation of S-adenosylmethionine decarboxylase was observed. Administration of methylglyoxal bis(guanylhydrazone) to castrated androgen-treated rats resulted in a marked increase in concentrations of all prostatic polyamines. Prostatic ornithine decarboxylase activity was nearly 2 times and adenosylmethionine decarboxylase activity 9 times higher than that of the testosterone-treated animals. In contrast with ventral prostate, methylglyoxal bis(guanylhydrazone) treatment inhibited moderately the accumulation of spermidine and spermine in seminal vesicle, although both ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were stimulated. Difluoromethylornithine inhibited significantly the weight gain of ventral prostate, but methylglyoxal bis(guanylhydrazone) produced a substantial increase in prostatic weight. These changes were largely due to the fact that the volume of prostatic secretion was greatly decreased by difluoromethylornithine, whereas methylglyoxal bis(guanylhydrazone) increased the amount of secretion. Treatment with difluoromethylornithine strikingly increased the methylglyoxal bis(guanylhydrazone) content of both ventral prostate and seminal vesicle, but even under these conditions the drug concentration remained low in comparison with other tissues. The results indicate that a combined use of these two polyamine anti-metabolites does not necessarily result in a synergistic growth inhibition of the androgen-induced growth of male accessory sexual glands.

Dataset Information

Bisphenol A modifies the regulation exerted by testosterone on 5 ? -reductase isozymes in ventral prostate of adult rats.

Publications

Bisphenol A modifies the regulation exerted by testosterone on 5 α -reductase isozymes in ventral prostate of adult rats.

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