The assessment of non-feminizing estrogens for use in neuroprotection

Kun Don Yi, Evelyn Perez, Shaohua Yang, Ran Liu, Douglas F. Covey, James W. Simpkins

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

Menopause is associated with a precipitous decline in circulating estrogens and a resulting loss of the neuroprotective actions of this steroid hormone. In view of the results of the Women's Health Initiative and the preceding knowledge that orally administered estrogens has a variety of adverse side effects, likely through actions on peripheral estrogen receptor alpha (ERα), we initiated a program of research to synthesis and assess a group of non-feminizing estrogens that lack ability to interact with ERs but retain much of the neuroprotective action of feminizing estrogens. This program of research is aimed at the identification of compounds which do not stimulate ERs but are potentially neuroprotective in vitro and in animal models of neuronal cell death. We discovered that the most effective non-feminizing estrogens were those with large bulky groups in the 2 and/or 4 carbon of the phenolic A ring of the steroid. These compounds were 8- to 114-fold more potent than 17 β-estradiol (βE2), but lacked ER binding capacity in vitro and feminizing effects in vivo. The success of this program of research suggests that strategies to optimize non-feminizing estrogens for use in postmenopausal women can be successful.

Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalBrain Research
Volume1379
DOIs
StatePublished - 16 Mar 2011

Fingerprint

Estrogens
Estrogen Receptor alpha
Steroids
Research
Women's Health
Menopause
Neuroprotection
Estradiol
Cell Death
Carbon
Animal Models
Hormones
In Vitro Techniques

Keywords

  • Estradiol
  • Estratrienes
  • Estrogen
  • Estrogen receptor
  • Estrone
  • Middle cerebral artery occlusion
  • Neuroprotection
  • Phenolic A ring
  • Structure-activity relationship

Cite this

Yi, Kun Don ; Perez, Evelyn ; Yang, Shaohua ; Liu, Ran ; Covey, Douglas F. ; Simpkins, James W. / The assessment of non-feminizing estrogens for use in neuroprotection. In: Brain Research. 2011 ; Vol. 1379. pp. 61-70.
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The assessment of non-feminizing estrogens for use in neuroprotection. / Yi, Kun Don; Perez, Evelyn; Yang, Shaohua; Liu, Ran; Covey, Douglas F.; Simpkins, James W.

In: Brain Research, Vol. 1379, 16.03.2011, p. 61-70.

Research output: Contribution to journalReview article

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