Beta carotene is the pigment
responsible for the orange color of carrots, pumpkins and other plants. An enzyme that converts the dietary carotenoid beta carotene into
vitamin A in the body may also regulate testosterone levels and growth
of the prostate, a new study found.
Scientists at the University of Illinois explored the impact of the
enzyme Bco1 on testosterone levels and testosterone-sensitive tissues
such as the prostate by comparing the prostatic function and
testosterone metabolism of mice that lacked functional copies of the
Bco1 gene with mice in the control group.
‘The loss of Bco1 enzyme significantly affects androgen synthesis and reduces AR signaling, decreasing cellular proliferation and growth of the prostate.’
In the body, Bco1 splits one molecule of beta carotene
to form two molecules of vitamin A. Scientists have hypothesized that
Bco1 might be involved in other biological processes as well, but the
current study is among the first to explore Bco1's activities beyond
"Previous studies have shown that mice lacking the Bco1 gene cannot
cleave beta carotene, and we also know that a lot of people carry
genetic variations in Bco1 that can affect their ability to metabolize
carotenoids," said the paper's lead author, Joshua W. Smith, who
conducted the research during his doctoral studies in nutritional
sciences at the U. of I.
"Similarly, it is possible that men with variations in their Bco1
gene may have altered testosterone levels, as we saw in the mice that
lacked Bco1," said Smith, currently a postdoctoral fellow at the Johns
Hopkins Bloomberg School of Public Health.
Both groups of mice were fed a diet free of beta carotene and other
carotenoids but which provided vitamin A to maintain normal levels of
that nutrient in their blood and livers.
As the researchers hypothesized, mice lacking Bco1 had lower blood
concentrations of testosterone. In examining the rodents' tissues, the
researchers found that the prostates were significantly smaller in mice
without the Bco1 gene.
These animals' prostates and seminal vesicles - both of which
require testosterone for normal development and maintenance - weighed 20
to 30% less than those of the other mice. The Bco1-null mice
also had 44% fewer Leydig cells in their testes - the cells that
convert cholesterol into testosterone.
Additionally, the mice without the Bco1 gene had 32% lower
levels of the Hsd17b3 gene, which is expressed exclusively in the Leydig
cells of the testes and is responsible for the final step of
In humans, hereditary mutations in the Hsd17b3 gene result in
deficient testosterone production and feminized male genitalia at birth.
In examining an array of 200 genes in the mice's prostates, the
researchers found 13 genes that were significantly altered by Bco1 loss -
including three genes involved in cell proliferation, one gene that
regulates the growth of stromal and epithelial tissues, two genes
associated with cell-cycle progression and one involved in cell death, a
process called apoptosis.
The scientists also found evidence that androgen receptor signaling
was disrupted in the mice without the Bco1 gene. AR signaling, which
regulates gene expression and is critical to the prostate's development
and function, also initiates and controls the progression of prostate
cancer, according to the study.
The findings suggest that the loss of Bco1 significantly affects
androgen synthesis and reduces AR signaling, decreasing cellular
proliferation and growth of the prostate, said senior author John W.
Erdman Jr., a professor emeritus of nutrition and food science at
In previous studies, the same researchers found that reducing
testosterone levels in the blood via castration significantly reduced
expression of many of the same cell growth and proliferation markers
that were reduced by Bco1 loss in the current study.
"These data support the hypothesis that androgen deprivation,
whether by castration or loss of Bco1, controls cellular proliferation
in the mouse prostate," Smith said. "The current study demonstrates that
while Bco1's primary function may be cleaving dietary carotenoids, this
enzyme also may impact other physiological processes that extend far
beyond carotenoid metabolism."