Mice lacking {beta}-carotene-15,15-dioxygenase exhibit reduced serum testosterone, prostatic androgen receptor signaling, and prostatic cellular proliferation

β-Carotene-15,15’-dioxygenase (BCO1) cleaves dietary carotenoids at the central 15,15’ double bond, most notably acting on β-carotene to yield retinal. However, Bco1 disruption also impacts diverse physiological end points independent of dietary carotenoid feeding, including expression of genes controlling androgen metabolism. Using the Bco1–/– mouse model, we sought to probe the effects of Bco1 disruption on testicular steroidogenesis, prostatic androgen signaling, and prostatic proliferation. Male wild-type (WT) and Bco1–/– mice were raised on carotenoid-free AIN-93G diets before euthanasia between 10 and 14 wk of age. Weights of the prostate and seminal vesicles were significantly lower in Bco1–/– than in WT mice (–18% and –29%, respectively). Serum testosterone levels in Bco1–/– mice were significantly reduced by 73%. Bco1 disruption significantly reduced Leydig cell number and decreased testicular mRNA expression of Hsd17b3, suggesting inhibition of testicular testosterone synthesis. Immunofluorescent staining of the androgen receptor (AR) in the dorsolateral prostate lobes of Bco1–/– mice revealed a decrease in AR nuclear localization. Analysis of prostatic morphology suggested decreases in gland size and secretion. These findings were supported by reduced expression of the proliferation marker Ki-67 in Bco1–/– prostates. Expression analysis of 200 prostate cancer- ...
Source: AJP: Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Hormones, Reproduction and Development Source Type: research