Signaling from the membrane via membrane estrogen receptor-α: Estrogens, xenoestrogens, and phytoestrogens

Cheryl S. Watson, Nataliya N. Bulayeva, Ann L. Wozniak, Celeste Finnerty

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Estrogen mimetics in the environment and in foods can have important consequences for endocrine functions. When previously examined for action via genomic steroid signaling mechanisms, most of these compounds were found to be very weak agonists. We have instead tested their actions via several membrane-initiated signaling mechanisms in GH3/B6 pituitary tumor cells extensively selected for high (responsive) or low (nonresponsive) expression of the membrane version of estrogen receptor-α (mERα). We found many estrogen mimetic compounds to be potently active in our quantitative extracellular-regulated kinase (ERK) activation assays, to increase cellular Ca++ levels, and to cause rapid prolactin release. However, these compounds may activate one or both mechanisms with different potencies. For instance, some compounds activate ERKs in both pM and nM concentration ranges, while others are only active at nM and higher concentrations. Compounds also show great differences in their temporal activation patterns. While estradiol causes a bimodal time-dependent ERK activation (peaking at both 3 and 30 min), most estrogen mimetics cause either an early phase activation, a late phase activation, or an early sustained activation. One xenoestrogen known to be a relatively potent activator of estrogen response element-mediated actions (bisphenol A) is inactive as an ERK activator, and only a modest inducer of Ca++ levels and prolactin release. Many different signaling machineries culminate in ERK activation, and xenoestrogens differentially affect various pathways. Clearly individual xenoestrogens must be individually investigated for their differing abilities to activate distinct membrane-initiated signal cascades that lead to a variety of cellular functions.

Original languageEnglish (US)
Pages (from-to)364-371
Number of pages8
JournalSteroids
Volume70
Issue number5-7 SPEC. ISS.
DOIs
StatePublished - May 2005

Fingerprint

Phytoestrogens
Estrogen Receptors
Estrogens
Phosphotransferases
Chemical activation
Membranes
Prolactin
Pituitary Neoplasms
Response Elements
Estradiol
Steroids
Food
Tumors
Assays
Cells

Keywords

  • Estradiol
  • Mechanism of action
  • Nongenomic
  • Steroid action

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Signaling from the membrane via membrane estrogen receptor-α : Estrogens, xenoestrogens, and phytoestrogens. / Watson, Cheryl S.; Bulayeva, Nataliya N.; Wozniak, Ann L.; Finnerty, Celeste.

In: Steroids, Vol. 70, No. 5-7 SPEC. ISS., 05.2005, p. 364-371.

Research output: Contribution to journalArticle

Watson, Cheryl S. ; Bulayeva, Nataliya N. ; Wozniak, Ann L. ; Finnerty, Celeste. / Signaling from the membrane via membrane estrogen receptor-α : Estrogens, xenoestrogens, and phytoestrogens. In: Steroids. 2005 ; Vol. 70, No. 5-7 SPEC. ISS. pp. 364-371.
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