Voltage-dependent K+ channel acts as sex steroid sensor in endocrine cells of the human ovary

Lars Kunz, Romi Rämsch, Annette Krieger, Kelly A. Young, Gregory Dissen, Richard Stouffer, Sergio Ojeda, Artur Mayerhofer

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Molecular targets of rapid non-genomic steroid actions are not well known compared to those of the classical transcription pathway, but ion channels have recently been identified to be steroid-sensitive. Especially, in the ovary, the very organ producing high amounts of sex steroids, their rapid actions are not well examined. We now identified a yet unknown target for sex steroids, a voltage-dependent K+ channel (KV4.2) that contributes to a transient outward K+ current (IA) in human granulosa cells (GCs). Sex steroid hormones at concentrations typical for the ovary (1 μM) blocked KV4.2 thereby attenuating IA by about 25% within seconds. We also found both KV4.2 (KCND2)mRNA and protein in endocrine cells of the human and rhesus macaque ovary, emphasizing the physiological relevance of this channel. Therefore, we propose a role as fast-responding steroid sensor for the KV4.2 channel. The direct regulation of K+ channel activity by sex steroids might represent a yet unknown mechanism of rapid steroid action in close proximity to the site of steroid production in the primate ovary. Our data might also be important for KV4 channels in the brain and the cardiovascular system where rapid steroid effects are discussed in the context of prevention of cell death.

    Original languageEnglish (US)
    Pages (from-to)167-174
    Number of pages8
    JournalJournal of Cellular Physiology
    Volume206
    Issue number1
    DOIs
    StatePublished - Jan 2006

    Fingerprint

    Endocrine Cells
    Ovary
    Steroids
    Cells
    Sensors
    Electric potential
    Cardiovascular system
    Granulosa Cells
    Gonadal Steroid Hormones
    Cell death
    Transcription
    Cardiovascular System
    Macaca mulatta
    Ion Channels
    Primates
    Brain
    Cell Death
    Messenger RNA

    ASJC Scopus subject areas

    • Clinical Biochemistry
    • Cell Biology
    • Physiology

    Cite this

    Voltage-dependent K+ channel acts as sex steroid sensor in endocrine cells of the human ovary. / Kunz, Lars; Rämsch, Romi; Krieger, Annette; Young, Kelly A.; Dissen, Gregory; Stouffer, Richard; Ojeda, Sergio; Mayerhofer, Artur.

    In: Journal of Cellular Physiology, Vol. 206, No. 1, 01.2006, p. 167-174.

    Research output: Contribution to journalArticle

    Kunz, Lars ; Rämsch, Romi ; Krieger, Annette ; Young, Kelly A. ; Dissen, Gregory ; Stouffer, Richard ; Ojeda, Sergio ; Mayerhofer, Artur. / Voltage-dependent K+ channel acts as sex steroid sensor in endocrine cells of the human ovary. In: Journal of Cellular Physiology. 2006 ; Vol. 206, No. 1. pp. 167-174.
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    abstract = "Molecular targets of rapid non-genomic steroid actions are not well known compared to those of the classical transcription pathway, but ion channels have recently been identified to be steroid-sensitive. Especially, in the ovary, the very organ producing high amounts of sex steroids, their rapid actions are not well examined. We now identified a yet unknown target for sex steroids, a voltage-dependent K+ channel (KV4.2) that contributes to a transient outward K+ current (IA) in human granulosa cells (GCs). Sex steroid hormones at concentrations typical for the ovary (1 μM) blocked KV4.2 thereby attenuating IA by about 25{\%} within seconds. We also found both KV4.2 (KCND2)mRNA and protein in endocrine cells of the human and rhesus macaque ovary, emphasizing the physiological relevance of this channel. Therefore, we propose a role as fast-responding steroid sensor for the KV4.2 channel. The direct regulation of K+ channel activity by sex steroids might represent a yet unknown mechanism of rapid steroid action in close proximity to the site of steroid production in the primate ovary. Our data might also be important for KV4 channels in the brain and the cardiovascular system where rapid steroid effects are discussed in the context of prevention of cell death.",
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