Developmental Changes in EH Protein Content/Activity
Few studies appear to have carefully
examined the ontogeny of mEH in the post-natal period compared to adults. Two studies (Cresteil et al., 1985;
Omiecinski et al., 1994) compared EH content and or activity in fetal livers
relative to adults. [1]
Cresteil et al. (1985) reported the mean ratio of fetal to adult EH content to
be about 23%. Omiecinski et al. (1994)
measured EH activity in fetal and adult liver and lung microsomes using the
substrate BP-4,5-oxide. EH activity in liver microsomes exhibited a linear
increase between gestational day 53 and day 153 (N=18). Median activity on days
130-153 was 68% that of 15 adults.
Ratanasavanh
et al. (1991) used immunoblotting
techniques to study the distribution and levels of epoxide hydrolase (in
addition to several P-450 enzymes) in
human livers from newborn (1 hour to 3 weeks), child (6 months to 11 years),
and adult (18-41 years) donors. Rather
than report the actual EH protein levels measured, the authors expressed the
protein levels relative to the level detected in a particular adult sample,
arbitrarily set to 1.[2] We have summarizes the mean relative values
by age groups (Table 4-6) In order to compare age groups directly as we have
for the other enzymes, the ratio of
these mean values relative to the group mean for adults is presented (last
column).
This analysis
suggests that EH levels in newborns and children are closer to adult levels
than were the fetal levels reported by Cresteil et al. (1985) but more similar
to the levels found in later gestational ages by Omiecinski et al (1994). Mean EH content was lowest in the 0-1 week
age group with the mean value being 69%
of the adult mean and appeared to increase in older children. However, the group means were not
statistically significant from one another, likely due to small sample size and
the high degree of variability in the results (Table 4-6).
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