title: The effect of 17beta estradiol withdrawal on the level of brain and peripheral neurosteroids in ovarectomized rats.
abstract: Dehydroepiandrosterone (DHEA), pregnenolone (P) and their sulfate derivatives are neuroactive neurosteroids synthesized endogenously in the brain and in steroidogenic organs and influence or are influenced by a variety of physiological processes. Since parturition is followed by a rapid drop in estrogen levels in serum and brain it may be hypothesized that the drastic drop in the brain exposure to estrogens may cause a disturbance in the neurosteroid-to-neurosteroid-sulfate equilibrium with clinical relevance. In order to develop a rat animal model for human postpartum rapid estrogen decline conditions, the present study investigated effects of sudden withdrawal of hyperphysiological estrogens levels on levels of DHEA, DHEAS, P and PS in peripheral blood and brain tissue as well as cortical sulfatase activity. Twenty-four 3-month-old female rats were ovarectomized followed by either no estrogen, high levels of estrogen alone, or followed by sudden withdrawal after high-administered estrogen levels. Results indicated elevated brain cortical DHEA-S and reduced cortical sulfatase in ovarectomized rats following sudden estrogen withdrawal. No significant alterations in DHEA, P or PS were noted. Study observations suggest the marked influence estrogen withdrawal states may have on cortical DHEA-S levels in particular, the precise mechanism of which remains unknown but which may be related to the paralleled decrease in sulfatase activity. This DHEA-S increase may lead to attenuated GABAergic tone and may be relevant to post-natal behavioral disturbances (e.g. depression, anxiety).
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Rabin Medical Center-Beilinson Campus, Petah Tikva 49100, Israel. rmayan@post.tau.ac.il
authors.forename: Rachel
authors.initials: R
authors.lastname: Maayan
authors.forename: Rael D
authors.initials: RD
authors.lastname: Strous
authors.forename: Machmoud
authors.initials: M
authors.lastname: Abou-Kaoud
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D010052:Ovariectomy; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000145:classification / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000378:metabolism*; D013429:Sulfatases / Q000378:metabolism
chemical_list: D013256:Steroids; D004958:Estradiol; D013429:Sulfatases