The effect of 17β estradiol withdrawal on the level of brain and peripheral neurosteroids in ovarectomized rats

Rachel Maayan, Rael D. Strous, MacHmoud Abou-Kaoud, Abraham Weizman

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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).

Original languageEnglish
Pages (from-to)156-161
Number of pages6
JournalNeuroscience Letters
Issue number1-2
StatePublished - 12 Aug 2005


  • DHEA
  • DHEA-S
  • Dehydroepiandrosterone
  • Neurosteroid
  • Postpartum
  • Pregnenolone


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