The effect of 17beta estradiol withdrawal on the level of brain and peripheral neurosteroids in ovarectomized rats.
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).
Maayan
Rachel
R
Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Rabin Medical Center-Beilinson Campus, Petah Tikva 49100, Israel. rmayan@post.tau.ac.il
Strous
Rael D
RD
Abou-Kaoud
Machmoud
M
Weizman
Abraham
A
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
D013256:Steroids; D004958:Estradiol; D013429:Sulfatases