Estradiol replacement elevates the serum and tissue levels of alpha-tocopherol in ovariectomized rats

Time-course changes in alpha-tocopherol (alpha TP) in serum and selected tissues were examined in ovariectomized rats with estradiol (ES) replacement. Female rats (242 +/- 7 g) were ovariectomized (day 0) and divided into two groups of five each; one group was implanted subcutaneously with a time-release ES pellet (OXE; 25 micrograms/day/rat) and the other with a placebo pellet (OXP). Rats were pair-fed twice daily a modified AIN-93G diet at 9:30 am and 4:30 pm. At day 0 and week 2, 4, and 6 of ES replacement, alpha TP, phospholipid (PL), and cholesterol in serum and HDL fraction were measured. HDL was isolated by affinity chromatography. ES produced a marked increase in total serum alpha TP and HDL cholesterol without affecting total serum cholesterol. The increase in serum alpha TP was caused by a selective increase in HDL alpha TP with no change in non-HDL alpha TP. HDL alpha TP in OXE rats was 10.3 +/- 0.8 micromole/L at day 0 and rose to 15.7 +/- 1.6 micromole/L at 2 wk with no further increase with time. alpha TP in the non-HDL fraction did not differ between groups. The alpha TP level in the non-HDL fraction was 11.1 +/- 2.0 micromole/L at day 0 and remained unchanged with time. The marked rise in HDL alpha TP in OXE rats was associated with a parallel increase in HDL PL (r = 0.80). The concentrations of alpha TP in the liver (103.4 +/- 12.1 nmol/g) and kidneys (52.1 +/- 3.6 nmol/g) of OXE rats were also significantly higher than those in the liver (74.4 +/- 14.4 nmol/g) and kidneys (21.1 +/- 2.2 nmol/g) of OXP rats. The results provide the first evidence that ES replacement at a physiological dose produces a marked increase in the body status of alpha TP. The finding may explain partly the inhibitory effect of ES on the oxidative modification of serum lipoproteins and elevation of serum HDL in response to ES replacement.