Estrogen deficiency alters peroxiredoxin levels in the bone and leads to redox signaling dysregulation in a rat menopause model

For decades, it has been known that estrogen deficiency induces reactive oxygen species (ROS) formation and that estrogen administration exerts beneficial actions by suppressing ROS in postmenopausal women as well as in ovariectomized animals. However, little is known about individual redox protein dysregulation and its implication in estrogen-sensitive tissues. Here, we evaluated levels and localization of key redox signaling components such as peroxiredoxins 1-6 (Prx1-6), Nrf-2, thioredoxin 1 (Trx1), and Keap1 in the bone marrow of ovariectomized (OVX) and intact rats with and without 17-β-estradiol replacement. We found that OVX-induced estrogen decline significantly decreased the levels of Prx2, Prx3, Prx4, Prx5, and Prx6 in the bone marrow and altered their expression pattern in several cell types of the bone. In addition, OVX increased the levels of secreted Prx1 and Prx2 in the bone marrow fluid. Furthermore, OVX induced upregulation of Keap1 in the bone marrow and increased levels of 8-OHdG both in the bone marrow and in the serum. Oral 17-β-estradiol administration for five days restored the levels of individual Prxs and was effective at reducing 8-OHdG levels in the bone marrow and in the serum of OVX rats. These findings suggest that estrogen deficiency causes oxidative damage by disrupting redox protein regulation and may provide guidance for future studies involving estrogen-deficient models.