paper presents preliminary suggestions that biphenol A may alter
circulating levels of ghrelin and leptin in wild mice. The experiment
was done in a way that does not allow testing for statistical significance
of the results. Hence all that can be concluded is that more attention
should focus on the role of compounds like BPA in disrupting the
hormonal control of weight regulation.
did they do? Nieminen et al. exposed sexually
mature mice to three different levels of bisphenol A and measured
circulating plasma levels of testosterone, ghrelin, leptin, estradiol,
cortisol, luteinizing hormone (LH)and thyroid stimulating hormone
(TSH); and activity levels of several liver and kidney enzymes.
Exposure levels for BPA were 10, 50, 0r 250 mg/kg, injected subcutaneously.
The mice were born to parents that had been caught in the wild.
experiment ran for 5 days, with injections the first 4. On the fifth,
the animals were sacrificed and examined. Blood samples and tissue
samples were taken immediately and after brief processing, stored
in liqud nitrogen.
serum samples obtained were too small to allow determination of
estradiol, LH, TSH, leptin, ghrelin and cortisol for individual
animals, so samples were pooled. This prevented statistical testing
for differences between treatment and control.
did they find? While none of the control animals died,
10 of the treated animals did, at least one from each exposure level,
indicating that these exposure levels are relatively high.
measurements suggested trends in response to increases in BPA exposure.
Plasma testosterone levels increased significantly. T4 levels did
not change. For the hormones whose analysis was based on pooled
samples, leptin levels appeared to decrease while ghrelin appeared
to increase. TSH did not change.
does it mean? Very little can be concluded about endocrine
disruption from these experiments. The deaths of treated animals
at these exposure levels indicate that wild mice of this species
are more sensitive to BPA than lab rats, for which comparable exposures
would not lead to mortality.
is the first report (contact
me if I am incorrect) of any study examining disruption of either
leptin or ghrelin hormone systems. The results are consistent with
an impact, but because of the statistical analysis nothing can be
concluded. That is unfortunate, because research into factors
disrupting weight homeostasis are greatly needed.
world is experiencing a global epidemic of obesity. Hormonal control
of weight homeostasis is a complex process involving a series of
hormonal systems. Indications like this that some of these systems
may be vulnerable to disruption should be pursued vigorously, particularly
on health issues of such global import. One of the recurring lessons
of research into endocrine disruption is that virtually
all chemically-mediated signaling systems are vulnerable.
and leptin are two of the hormone systems important to weight homeostasis:
secreted by the stomach, ghrelin increases food intake and decreases
fat breakdown (lipolysis). Leptin is produced by fat cells. Normally
more fat leads to more leptin, which then represses appetite and
increases basal metabolic rate. The direction of BPA's impact on
these two systems (leptin down, ghrelin up) suggested by Nieminen
et al.'s work is thus consistent with a pattern that would
lead to weight gain. Their experiments ran only a short time, however.
would make more sense for the initial entry into this research field
to focus on in utero exposures at low levels, not high
level exposures of adults. Howdeshell's
work, for example, on changes in the rate of sexual development
following in utero exposure to BPA were conducted at exposure
levels 1000-times lower; and indeed she found a significant effect
of in utero exposure on pubertal weight: exposed animals
were significantly heavier. That study did not examine either ghrelin
or leptin levels; indeed ghrelin had not even been discovered.