Mechanisms of membrane estrogen receptor-α-mediated rapid stimulation of Ca2+ levels and prolactin release in a pituitary cell line

Nataliya N. Bulayeva, Ann L. Wozniak, L. Leanne Lash, Cheryl S. Watson

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


The role of membrane estrogen receptor-α (mERα) in rapid nongenomic responses to 17β-estradiol (E2) was tested in sublines of GH3/B6 rat prolactinoma cells selected for high (GH3/ B6/F10) and low (GH3/B6/D9) mERα expression. E2 elicited rapid, concentration-dependent intracellular Ca2+ concentration ([Ca 2+]i) increases in the F10 subline. Lack of inhibition by thapsigargin depletion of intracellular Ca2+ pools, together with abrogation of the response in Ca2+-free medium, suggested an extracellular source of Ca2+ for this response. The participation of voltage-dependant channels in the E2-induced [Ca2+] i increase was confirmed by the specific L-type Ca2+ channel inhibitor nifedipine. For comparison, the D9 mERα-depleted subline was insensitive to steroid action via this signaling mechanism. [Ca 2+]i elevation was correlated with prolactin (PRL) release in the F10 cell line in as little as 3 min. E2 caused a much higher PRL release than KCl treatment (which caused maximal Ca2+ elevation), suggesting that secretion was also controlled by additional mechanisms. Participation of mERα in these effects was confirmed by the ability of E2-peroxidase (a cell-impermeable analog of E2) to cause these responses, blockage of the responses with the ER antagonist ICI 182 780, and the inability of the E2 stereoisomer 17α-E2 to elicit a response. Thus rapid exocytosis of PRL is regulated in these cells by mERα signaling to specific Ca2+ channels utilizing extracellular Ca2+ sources and additional signaling mechanisms.

Original languageEnglish (US)
Pages (from-to)E388-E397
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2 51-2
StatePublished - Feb 2005


  • Exocytosis
  • Intracellular Ca
  • L-type channel
  • Prolactinoma cell line

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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