Estrogen regulates β1-subunit expression in Ca 2+-activated K+ channels in arteries from reproductive tissues

Deepa Nagar, Xiao Tie Liu, Charles R. Rosenfeld

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Daily estradiol-17β (E2β) increases basal uterine blood flow (UBF) and enhances acute E2β-mediated increases in UBF in ovariectomized nonpregnant ewes. The acute E2β-mediated rise in UBF involves vascular smooth muscle (VSM) large-conductance Ca 2+-activated K+ channels (BKCa). BK ca consist of pore-forming α-subunits and regulatory β1-subunits that modulate channel function and E 2β responsiveness. It is unclear whether E2β also alters subunit expression and thus channel density and/or function, thereby contributing to the rise in basal UBF and enhanced UBF responses that follow daily E2β. Therefore, we examined BKca subunit expression by using reverse transcription-PCR and immunoblot analysis of arterial VSM from reproductive and nonreproductive tissues and myometrium from ovariectomized nonpregnant ewes after daily E2β (1 μg/kg iv) or vehicle without or with acute E2β (1 μg/kg). Tissue distribution was determined by immunohistochemistry. Acute E2β did not alter α- or β1-subunit expression in any tissue (P > 0.1). Daily E2β also did not affect α-subunit mRNA or protein in any tissue (P > 0.1) or mesenteric arterial VSM β1-subunit. However, daily E2β increased uterine and mammary arterial VSM β1-subunit mRNA by 32% and 83% (P < 0.05), uterine VSM protein by 30%, and myometrial β1-subunit mRNA and protein by 74% (P < 0.005). Immunostaining of uterine arteries, myometrium, and intramyometrial arteries paralleled immunoblot analyses for both subunits. Although BKCa density is unaffected by daily and acute E2β, daily E2β increases β1- subunit in proximal and distal uterine arterial VSM. Thus prolonged E 2β exposure may alter BKca function, estrogen responsiveness, and basal vascular tone and reactivity in reproductive arteries by modifying α:β1 stoichiometry.

Original languageEnglish (US)
Pages (from-to)H1417-H1427
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number4 58-4
DOIs
StatePublished - Oct 2005

Keywords

  • Mammary artery
  • Mesenteric artery
  • Myometrium
  • Nonpregnant ewes
  • Uterine blood flow
  • Vasodilation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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