Estrogen transiently increases delayed rectifier, voltage-dependent potassium currents in ovine gonadotropes.
Treatment of gonadotropes with estrogen (E) changes the electrophysiological response to gonadotropin-releasing hormone (GnRH) such that the cells are hyperpolarised immediately after stimulation with GnRH and then generate action potentials more frequently than non-E-treated cells. We investigated the role of K+ current in this altered response to GnRH using cultures of ewe pituitary cells enriched for gonadotropes. K+ current density was measured using nystatin-perforated whole-cell recordings in the voltage clamp mode. Treatment of cells with E for 16-20 h significantly (p < 0.01) increased the unit K+ current to 180% of that in vehicle-treated cells. Outward current in these cells flows predominantly through voltage-dependent, delayed rectifier K+ channels (IK), and E alters the magnitude of this current. The effect of E to increase the K+ current was dose- and time-dependent and was maximal after 16-20 h. The unit K+ current values returned to pre-treatment levels after 36 h of E treatment. Several cells were studied both before and after E treatment and the average effect of E on these cells was to increase the unit K+ current by 90%. The time-course of the effect of E on K+ current density is the same as the effect of E to increase LH release in vitro and in vivo. We conclude that the increase in K+ current may be an important part of the mechanism whereby E acts on gonadotropes to facilitate the LH surge which triggers ovulation.
Cowley
M A
MA
Prince Henry's Institute of Medical Research, Monash Medical Centre, Clayton, Vic., Australia.
Chen
C
C
Clarke
I J
IJ
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007700:Kinetics; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D012756:Sheep
D002121:Calcium Channel Blockers; D004967:Estrogens; D015221:Potassium Channels; D007987:Gonadotropin-Releasing Hormone; D002118:Calcium