| |
|
|
 |
|
Advisory Committee on Health Effects of Endocrine Disruptors
The Supplement II to the Intermediary Report
1.3.2 |
| |
contents
Detailed contents
<< prev
next >> |
| |
Irreversible effects of agents on organisms at the embryonic,
fetal and neonatal stages were noted in Global Assessment, and
reports related to this topic continue to appear. The major
issues in this field are the expression of hormone receptors at
these stages and related species differences. For example, study
on the expression of hormone receptors in neonatal male rats
revealed that ERs are expressed in all the cells in which
androgen receptors (ARs) have been expressed in the
developmental stage. ERβs are expressed earlier than AR in
Sertoli cells, and ERβs are expressed but ARs are not in most
fetal blast cells including genital cells. These observations
have an important implication in the response of the organism to
exogenous endocrine disruptors29.
Considering the difference in the mode of expression between
humans and experimental animals, some researchers question the
possibility of expression in humans, exposed to higher levels of
natural estrogen, to that in mice or rats associated with rather
low levels of exogenous hormone-like substances30.
On the other hand, however, it is claimed that there is no
reason to assume that the effects of BPA is lower in humans than
in mice or rats, based on a study of molecular species
associated with RXRs in humans and rats31.
More studies are needed to resolve this discrepancy. As for male
genital organs, highly TGFα-positive squamous metaplasia induced
by 10-9 M estradiol was reported32.
The metaplasia is believed to be caused by TGFα which is induced
via ERα in the prostate, but details are not clear. |
| |
29 Williams K, McKinnell C, Saunders PTK,
Walker M, Fisher JS, Turner KJ, Atanassova N, SharpeRM：Neonatal
exposure to potent and environmental oestrogens and
abnormalities of the male reproductive system in the rat:
evidence for importance of the androgen-oestrogen balance and
assessment of the relevance to man, Human Reproduction Update 7,
3 (2001) 236-247
30 Witorsch RJ: Low-dose in utero
effects of xenoestrogens in mice and their relevance to humans:
an analytical review of the literature, Food and Chemical
Toxicology 40(2002)905-912
Based on endocrinologic differences between pregnant humans and
mice, including the place and time of production and
transformation of sex hormones as well as their concentrations
and mode of existence, it is suggested that effects on the
reproductive system or effects of BPA at low doses observed in
mice would not appear in humans. While rats and mice produce
estradiol and estron, humans produce estriol in addition to
them. Furthermore, the blood estradiol level in human mothers in
the late pregnancy is 15-20 ng/ml, which is several hundred
times higher than that in rats and mice (30-60 pg/ml). Similarly
the concentration in the fetus is 5-10 mg/ml in humans and
100-150 pg/ml in mice. In addition, the human fetus
shows high levels of estron (10-15 ng/ml) and estriol (50-100 ng/ml)
in late pregnancy of the mother. Sex differentiation of humans
starts in the 7th-14th week of pregnancy (with estradiol level
of 2-6 ng/ml in the fetal blood), which compares with 15th day
of fetal age or later (with estradiol level of 100-150 pg/ml in
the fetal blood). The level of free form estradiol in fetal
plasma of humans is 1-4.5%, while that in mouse plasma is
estimated to be 0.2%.
31 Bruce Blumberg: Unpublished data.
32 Health and Labor Research report
(Inoue's group), unpublished data. |
|
contents
Detailed contents
<< prev
next >> |
|
|
|
