title: Activity-dependent modulation of gonadotrophin-releasing hormone neurone activity by acute oestradiol.
abstract: Oestradiol (E₂) exerts potent feedback actions upon gonadotrophin-releasing hormone (GnRH) neurones and part of this feedback action may occur through the rapid action of E₂. Using a transgenic GnRH-Pericam mouse line that allows real-time intracellular calcium concentrations ([Ca²⁺](i)) to be monitored in adult GnRH neurones in a brain slice preparation, we examined the acute effects of 100 pM-100 nM E₂ on [Ca²⁺](i) transients in spontaneously active GnRH neurones. Approximately 30% of GnRH neurones exhibit spontaneous [Ca²⁺](i) transients at a frequency greater than two transients/15 min in adult female mice. In these cells, treatment with an incremental 1, 10, 100 nM E₂ protocol or 100 pM E₂ alone resulted in the suppression or complete cessation of [Ca²⁺](i) transients in 15 of 18 (83%) GnRH neurones. This effect was mimicked by E₂ bound to albumin, suggesting a membrane site of action, and was maintained in oestrogen receptor β knockout mice, indicating that this receptor is not essential for the rapid suppression of [Ca²⁺](i) transients. These findings contrast with those GnRH neurones exhibiting very few or no [Ca²⁺](i) transients (< 2 transients/15 min) that exhibit the opposite response of being activated by acute E₂. A series of dual calcium-cell-attached electrical recordings showed that [Ca²⁺](i) transients were associated with GnRH neurone burst firing and that E₂ suppression or activation of [Ca²⁺](i) transients was mirrored by a depression or initiation of burst firing. Taken together, these studies demonstrate that the acute actions of E₂ on GnRH neurones are critically dependent upon their pattern of burst firing.
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionelle, Montpellier, France.
authors.forename: Nicola
authors.initials: N
authors.lastname: Romanò
authors.forename: Allan E
authors.initials: AE
authors.lastname: Herbison
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology; D020013:Calcium Signaling / Q000187:drug effects; D055724:Electrophysiological Phenomena / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques
chemical_list: D000418:Albumins; D047629:Estrogen Receptor beta; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol