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A folic acid‐enriched diet attenuates prostate involution in response to androgen deprivation
Author(s) -
Joseph Diya B.,
Chandrashekar Anoop S.,
Chu LiFang,
Thomson James A.,
Vezina Chad M.
Publication year - 2019
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23723
Subject(s) - endocrinology , medicine , involution (esoterism) , androgen , prostate , castration , testosterone (patch) , prostate cancer , androgen deprivation therapy , biology , hormone , consciousness , cancer , neuroscience
Background Serum folate concentrations in the United States have risen since dietary folic acid fortification was first mandated in 1998. Although maternal folic acid offers protection against neural tube defects in conceptuses, its impact on other organ systems and life stages have not been fully examined. Here, we used a mouse model to investigate the impact of a Folic acid (FA) enriched diet on prostate homeostasis and response to androgen deprivation. Methods Male mice were fed a control diet (4 mg FA/kg feed) or a folic acid supplemented diet (24 mg FA/kg feed) beginning at conception and continuing through early adulthood, when mice were castrated. Results We made the surprising observation that dietary FA supplementation confers partial resistance to castration‐mediated prostate involution. At 3, 10, and 14 days post‐castration, FA enriched diet fed mice had larger prostates as assessed by wet weight, taller prostatic luminal epithelial cells, and more abundant RNAs encoding prostate secretory proteins than castrated control diet fed mice. Diet did not significantly affect prostate weights of intact mice or serum testosterone concentrations of castrated mice. RNA‐Seq analysis revealed that the FA enriched diet was associated with a unique prostate gene expression signature, affecting several signaling and metabolic pathways. Conclusions Continuous exposure to a FA enriched diet slows prostate involution in response to androgen deprivation. Prostates from FA diet mice have increased secretory gene expression and increased luminal cell heights. The influence of dietary FA supplementation on the prostate response to androgen deprivation raises a future need to consider how dietary folic acid supplementation affects efficacy of androgen‐reducing therapies for treating prostate disease.