In the present study the effect of diets restricted in either zinc or pyridoxine upon
estrogen directed gene expression in the mature rat uterus was tested. Sexually mature
female rats were maintained on zinc-adequate (40 mg/kg diet) ad libitum or restricted-fed,
pyridoxine-deficient, or zinc-deficient ( < 1 mg/kg diet or 3mg/kg diet) ad libitum-fed diets
for 35 days. All animals were bilaterally ovariectomized and used for experimentation
at 14 days post ovariectomy. On day 35 each rat was injected intraperitoneally with
estrogen. They were killed at different times post injection and thymidine kinase (TK,
EC 2.7.1.21) or creatine kinase (CK, EC 2.7.3.2) activity was assayed in uteri cytosol
fractions. In addition the steady state level of ckb mRNA in uteri cytosol fractions was
measured following estrogen administration.
The weight gain of the rats fed the low zinc and low pyridoxine diets was significantly
lower than those fed the zinc-adequate diet ad libitum. The consumption of the
zinc-deficient diet resulted in a significant decrease in plasma zinc while a pyridoxine
deficient diet produced a significant reduction in plasma pyridoxine.
Vehicle-injected uterine TK activity was 2-3 pmoles of d-TMP/min/mg protein.
The TK activity was significantly increased (p < 0.05) 42 h post estrogen injection on the
zinc-adequate diet ad libitum and pair-wt fed rats. This activity was sustained at 48 h
post injection prior to declining to control values within 60 h. The maximum (4-fold)
increase occured at 36 h post estrogen injection in pyridoxine-deficient rats which was
sustained at 42 & 48 h. The increase in uterine TK activity was 3-fold at 42 hand 48 h
post injection. However this increase was not significantly different from the peak value
seen in zinc-adequate and pyridoxine-deficient diet fed rats.
No measureable effect of estrogen on CK activity was observed on the zincadequate
or zinc-deficient diet fed rats using a coupled enzyme assay. However the time
course of ckb mRNA induction on the zinc-adequate pair-wt fed rats following estrogen
administration paralleled the time course of estrogen induced protein (IP) synthesis
previously observed by Gorski et al. (1970). IP is now known to be the brain type
isoenzyme of creatine kinase. An induction of ckb mRNA between 0-3 h post estrogen
injection was not observed on the zinc-deficient diet fed rats. However in a subsequent
experiment an induction of uterine ckb mRNA 2 h following estrogen administration
was observed in zinc-deficient rats. The possible reasons for this discrepancy are discussed.
Zinc ions are known to be required to enable the estrogen receptor complex to
bind to DNA and initiate transcription. It has been hypothesized that inadequate provision
of dietary zinc may therefore reduce compliance to estrogen directed gene expression
by limiting the efficiency of recruitment of zinc ions for stabilization of the zinc
finger of the steroid receptor. The results of the present study failed to support this hypothesis
at this moderate level of zinc depletion.
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