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) <i>ad libitum</i> or restricted-fed, pyridoxine-deficient, or zinc-deficient ( < 1 mg/kg diet or 3mg/kg diet) <i>ad libitum</i>-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 <i>ckb</i> 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 <i>ad libitum</i> 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 occurred 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 measurable effect of estrogen on CK activity was observed on the zinc adequate 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 <i>ckb</i> 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. / Ph. D.

M. S.

M. S.

"August 2002" / Bibliography: leaves 141-176. / ix, 179 leaves : ill. (some col.) ; 30 cm / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Changes in maternal-foetal zinc homeostasis resulting in a foetal deficiency may be an important contributing factor in ethanol-realted teratogenicity. Ethanol induces expression of hepatic metallothionein, causing zinc transfer from the plasma to the liver. Rodent studies show that changes in plasma zinc correlate with a high incidence of abnormal fetuses in MT+/+ mice. Demonstrates a clear link between maternal hepatic MT induction, decreased foetal zinc supply, and teratogenicity, which has major implications for binge alcohol consumption in early pregnancy. The demonstration that zinc treatment is effective in preventing teratogenicity indicates potential treatment strategies. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2003

The function of zinc in the nutrition of man has been studied by numerous investigators in an attempt to determine the needs of the body for this element. To date no deficiency disease has been produced by a zinc-deficient diet and cured by the addition of this element to the diet. The only criteria thus far presented to establish its essentialness in the dietary of man are the facts that zinc is retained by the body and that its presence is necessary for normal functioning of other nutrients. This study was made to observe zinc metabolism of young college women on self-selected diets, to see if a requirement for zinc intake in humans could be established.

To study the effect of exercise and protein intake during pregnancy on maternal and fetal zinc status in the rat, one hundred and seventy-nine pregnant Sprague-Dawley rats were divided into four groups; sedentary-standard protein diet, sedentary-high protein diet, exercising-standard protein diet and exercising-high protein diet. The standard protein diet contained 7.22% protein, while the high protein diet contained 24.77% protein; all other nutrients were supplied in amounts required for normal parturition of the laboratory rat. After acclimatization, the exercising dams, regardless of diet, were made to swim continuously for one and one-half hours/day until sacrifice. The four major groups were further subdivided into 28 groups, designated by three-day intervals according to gestational day--days 3, 6, 9, 12, 15, 18, and 21. Uterine tissues were retained for zinc content analysis; fetal and placental tissues were separated from uterine tissue for days 15 through 21 only. The concentration of uterine zinc was affected solely by gestation; absolute placental tissue zinc values were lowest in the sedentary-high and exercising-low protein groups, while the exercising-high protein group possessed the greatest zinc value. No significant difference was detected in fetal zinc concentrations. Fetal tissue from exercising dams weighed significantly less (p<0.05) than fetal tissue from the sedentary dams; and sedentary-high protein dams produced significantly more (p<0.05) fetuses than the exercising-high protein dams. Both protein intake and exercising during pregnancy significantly affect normal parturition and zinc metabolism in the rat. / M.S.