Synthesis and turnover of ceruloplasmin in rats treated with 17 beta-estradiol

The effects of estrogen on synthesis and turnover of ceruloplasmin were studied in adult female Fischer rats. Daily treatment with 140 microgram 17 beta-estradiol resulted in a slow rise of ceruloplasmin concentrations, as measured by p-phenylenediamine oxidase activity, leading to a 70% increase by 7 days and a tripling by Day 14. Ceruloplasmin protein concentrations increased to the same degree, based on yields of the protein obtained during purification. Effects of estrogen on rates of synthesis (incorporation of [3H]leucine) were followed, using immunoprecipitation of total ceruloplasmin or isolation of its two major isoforms (Rfs 0.4 and 0.6 in native gel electrophoresis). Synthesis was increased by 7 days and was 2.5 times that of controls by Day 14. Both forms of ceruloplasmin showed the same specific activities and degree of increase in rate of synthesis. Rates of ceruloplasmin turnover were unaffected, based on double labeling with 3H- and 14C-leucine, but were three- to fourfold faster than for total plasma protein. The enzymatically more active 0.6 Rf form of ceruloplasmin had a faster turnover rate than the 0.4 Rf form. Estrogen treatment doubled ceruloplasmin mRNA levels by 7 days and almost tripled them by Day 14. Most of the ceruloplasmin mRNA was associated with the endoplasmic reticulum-bound polyribosomes. We conclude that estrogen increases the rate of synthesis of two forms of ceruloplasmin by indirectly increasing liver concentrations of its mRNA but has no effect on ceruloplasmin turnover.