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

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 (I(A)) in human granulosa cells (GCs). Sex steroid hormones at concentrations typical for the ovary (1 microM) blocked Kv4.2 thereby attenuating I(A) 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.

Peritubular myoid cells have a role in postnatal testicular growth

“…Labeling of nuclei was done as described previously 30 . Mitotic events were expressed as percentage of DAPI stained nuclei.…”

Testosterone Relaxes Isolated Human Radial Artery by Potassium Channel Opening Action

“…Different studies in humans and animals have used different solvents in different concentrations (e.g, ethanol and dimethysulphoxide). Solvents have unselective effects on ion channel activity (46), within miliseconds, which could interfere with the selective actions of testosterone. In previous studies however, no significant relaxant effect of final concentrations of the solvents has been reported (13, 14, 22 -26, 34, 35).…”

Vasodilating Mechanisms of Testosterone

“…ethanol and dimethysulphoxide). Solvents have unselective effects on ion channel activity ( Kunz et al, 2006 ), within miliseconds, which could interfere with selective actions of testosterone. In previous studies however, no signifi cant relaxant effect of fi nal concentrations of the solvents has been reported ( Yue et al, 1995 ;Chou et al, 1996 ;Costarella et al, 1996 ;Honda et al, 1999 ;English et al, 2000d , Ding andTep-areenan et al, 2002 ;Jones et al, 2002 ;Tep-areenan et al, 2003 ).…”