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 journalArticle

    55 Citations (Scopus)

    Abstract

    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
    Volume22
    Issue number9
    DOIs
    StatePublished - Sep 2008

    Fingerprint

    estriol
    Cell signaling
    Estriol
    estrone
    Estrone
    Cell proliferation
    Pituitary Neoplasms
    estrogens
    estradiol
    Tumors
    Estradiol
    Estrogens
    Cell Proliferation
    hormones
    Hormones
    Calcium
    calcium
    Chemical activation
    Biological Phenomena
    Calcium Signaling

    Keywords

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

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences (miscellaneous)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Biochemistry
    • Cell Biology

    Cite this

    Nongenomic actions of estradiol compared with estrone and estriol in pituitary tumor cell signaling and proliferation. / Watson, Cheryl S.; Jeng, Yow Jiun; Kochukov, Mikhail Y.

    In: FASEB Journal, Vol. 22, No. 9, 09.2008, p. 3328-3336.

    Research output: Contribution to journalArticle

    Watson, Cheryl S. ; Jeng, Yow Jiun ; Kochukov, Mikhail Y. / Nongenomic actions of estradiol compared with estrone and estriol in pituitary tumor cell signaling and proliferation. In: FASEB Journal. 2008 ; Vol. 22, No. 9. pp. 3328-3336.
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