Abstract
We report the first study of voltage-activated and GnRH-induced plasma membrane currents and their modulation by estradiol (E2) in mouse gonadotrophs. In consideration of the pleiotropic effects of E2 on gonadotrophin secretion and the relationship between plasma membrane electrical excitability and secretion, our objective was to determine the role of E 2 in modulating gonadotroph plasma membrane currents. We measured total voltage-activated and GnRH-induced currents using the perforated-patch configuration of the patch-clamp technique, which preserves signaling pathways, including GnRH-induced Ca2+ oscillations. We show that female mouse gonadotrophs are similar to those from other species in that the voltage-activated net current response exhibits an inward fast activating current that is inhibited by tetrodotoxin, which is characteristic of a Na + current, and a larger magnitude outward current with a profile suggesting the presence of multiple K+ currents. Furthermore, in voltage-clamped mouse gonadotrophs, GnRH activates large amplitude current oscillations that are apamin sensitive and have a reversal potential of -90 mV, consistent with Ca2+-activated K+ currents. Significantly, E2 pretreatment for 2-5 d decreased the density of both the peak outward voltage-activated current and the peak GnRH-induced current. The specific linkage between the observed E2 effects on membrane currents and, ultimately, gonadotroph function remains to be established. However, because decreased K+ current density is associated with an increase in membrane electrical excitability, we postulate increased excitability is one of the modes of action of E2 in sensitizing the gonadotroph to GnRH, an event central to the regulation of cyclic gonadotrophin secretion.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5798-5805 |
| Number of pages | 8 |
| Journal | Endocrinology |
| Volume | 147 |
| Issue number | 12 |
| DOIs | |
| State | Published - 2006 |
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ASJC Scopus subject areas
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
Estradiol inhibition of voltage-activated and gonadotropin-releasing hormone-induced currents in mouse gonadotrophs. / Waring, Dennis W.; Turgeon, Judith L.
In: Endocrinology, Vol. 147, No. 12, 2006, p. 5798-5805.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Estradiol inhibition of voltage-activated and gonadotropin-releasing hormone-induced currents in mouse gonadotrophs
AU - Waring, Dennis W.
AU - Turgeon, Judith L
PY - 2006
Y1 - 2006
N2 - We report the first study of voltage-activated and GnRH-induced plasma membrane currents and their modulation by estradiol (E2) in mouse gonadotrophs. In consideration of the pleiotropic effects of E2 on gonadotrophin secretion and the relationship between plasma membrane electrical excitability and secretion, our objective was to determine the role of E 2 in modulating gonadotroph plasma membrane currents. We measured total voltage-activated and GnRH-induced currents using the perforated-patch configuration of the patch-clamp technique, which preserves signaling pathways, including GnRH-induced Ca2+ oscillations. We show that female mouse gonadotrophs are similar to those from other species in that the voltage-activated net current response exhibits an inward fast activating current that is inhibited by tetrodotoxin, which is characteristic of a Na + current, and a larger magnitude outward current with a profile suggesting the presence of multiple K+ currents. Furthermore, in voltage-clamped mouse gonadotrophs, GnRH activates large amplitude current oscillations that are apamin sensitive and have a reversal potential of -90 mV, consistent with Ca2+-activated K+ currents. Significantly, E2 pretreatment for 2-5 d decreased the density of both the peak outward voltage-activated current and the peak GnRH-induced current. The specific linkage between the observed E2 effects on membrane currents and, ultimately, gonadotroph function remains to be established. However, because decreased K+ current density is associated with an increase in membrane electrical excitability, we postulate increased excitability is one of the modes of action of E2 in sensitizing the gonadotroph to GnRH, an event central to the regulation of cyclic gonadotrophin secretion.
AB - We report the first study of voltage-activated and GnRH-induced plasma membrane currents and their modulation by estradiol (E2) in mouse gonadotrophs. In consideration of the pleiotropic effects of E2 on gonadotrophin secretion and the relationship between plasma membrane electrical excitability and secretion, our objective was to determine the role of E 2 in modulating gonadotroph plasma membrane currents. We measured total voltage-activated and GnRH-induced currents using the perforated-patch configuration of the patch-clamp technique, which preserves signaling pathways, including GnRH-induced Ca2+ oscillations. We show that female mouse gonadotrophs are similar to those from other species in that the voltage-activated net current response exhibits an inward fast activating current that is inhibited by tetrodotoxin, which is characteristic of a Na + current, and a larger magnitude outward current with a profile suggesting the presence of multiple K+ currents. Furthermore, in voltage-clamped mouse gonadotrophs, GnRH activates large amplitude current oscillations that are apamin sensitive and have a reversal potential of -90 mV, consistent with Ca2+-activated K+ currents. Significantly, E2 pretreatment for 2-5 d decreased the density of both the peak outward voltage-activated current and the peak GnRH-induced current. The specific linkage between the observed E2 effects on membrane currents and, ultimately, gonadotroph function remains to be established. However, because decreased K+ current density is associated with an increase in membrane electrical excitability, we postulate increased excitability is one of the modes of action of E2 in sensitizing the gonadotroph to GnRH, an event central to the regulation of cyclic gonadotrophin secretion.
UR - http://www.scopus.com/inward/record.url?scp=33751521623&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751521623&partnerID=8YFLogxK
U2 - 10.1210/en.2006-1112
DO - 10.1210/en.2006-1112
M3 - Article
C2 - 16946005
AN - SCOPUS:33751521623
VL - 147
SP - 5798
EP - 5805
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 12
ER -