The molecular mechanisms involved in the regulation of synaptic plasticity and neuroprotection by estradiol (E(2)) and progesterone (P(4)) are unknown. Because these processes involve changes in cytoskeleton organization, we studied the effects of E(2) and P(4) in the expression of two cytoskeletal proteins: microtubule associated protein 2 (MAP2) and tau in the hippocampus and the frontal cortex of ovariectomized adult rats. While tau expression was unaffected by E(2) and P(4), an increase in MAP2 protein content in the hippocampus but not in the cortex was observed after E(2) and P(4) treatments. Interestingly, these steroids did not modify MAP2 mRNA content in the hippocampus. These data suggest that MAP2 is involved in the structural changes induced by E(2) and P(4) in the rat hippocampus, and that MAP2 expression is regulated by these steroid hormones at a postranscriptional level.