Nongenomic actions of estradiol compared with estrone and estriol in pituitary tumor cell signaling and proliferation

Cheryl S. Watson, Yow Jiun Jeng, Mikhail Y. Kochukov

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Physiological estrogens, including estrone (E1), estradiol (E2), and estriol (E3), fluctuate with life stage, suggesting specific roles for them in biological and disease processes. We compared their nongenomic signaling and functional actions in GH3/B6/ F10 rat pituitary tumor cells. All hormones caused prolactin release at 1 min; the lowest effective concentrations were 10-11 M E2, 10 -10 M E1, and 10-7 M E3. All estrogens increased the oscillation frequency of calcium (Ca) spikes, with the same time delay (∼200 s) at all levels (10-15 to 10-9 M). At some concentrations, E1 and E3 provoked more Ca-responding cells than E2. The amplitude and volume of Ca peaks were elevated by all hormones at ≥10-15 M. All hormones caused cell proliferation, with the lowest effective concentrations of E2 (10-15 M) > E1 (10-12 M) > E3 (10-10 M); E2 caused higher maximal cell numbers at most concentrations. All estrogens caused oscillating extracellular-regulated kinase (ERK) activations, with relative potencies of E1 and E2 > E3. All estrogens were ineffective in activation of ERKs or causing proliferation in a subline expressing low levels of membrane estrogen receptor-α. Dose-response patterns were frequently nonmonotonic. Therefore, the hormones E1 and E3, which have been designated "weak" estrogens in genomic actions, are strong estrogens in the nongenomic signaling pathways and functional responses in the pituitary.

Original languageEnglish (US)
Pages (from-to)3328-3336
Number of pages9
JournalFASEB Journal
Issue number9
StatePublished - Sep 2008
Externally publishedYes


  • Calcium
  • ERK activation
  • Membrane estrogen receptors
  • Nonmonotonic dose responses
  • Prolactin release

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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