Regulation of endogenous conductances in GnRH neurons by estrogens.
17β-estradiol (E2) regulates the activity of the gonadotropin-releasing hormone (GnRH) neurons through both presynaptic and postsynaptic mechanisms, and this ovarian steroid hormone is essential for cyclical GnRH neuronal activity and secretion. E2 has significant actions to modulate the mRNA expression of numerous ion channels in GnRH neurons and/or to enhance (suppress) endogenous conductances (currents) including potassium (K(ATP), A-type) and calcium low voltage T-type and high voltage L-type currents. Also, it is well documented that E2 can alter the excitability of GnRH neurons via direct action, but the intracellular signaling cascades mediating these actions are not well understood. As an example, K(ATP) channels are critical ion channels needed for maintaining GnRH neurons in a hyperpolarized state for recruiting T-type calcium channels that are important for burst firing in GnRH neurons. E2 modulates the activity of K(ATP) channels via a membrane-initiated signaling pathway in GnRH neurons. Obviously there are other channels, including the small conductance activated K(+) (SK) channels, that maybe modulated by this signaling pathway, but the ensemble of mER-, ERα-, and ERβ-mediated effects both pre- and post-synaptic will ultimately dictate the excitability of GnRH neurons.
Rønnekleiv
Oline K
OK
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR 97239, USA. ronnekle@ohsu.edu
Bosch
Martha A
MA
Zhang
Chunguang
C
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D025461:Feedback, Physiological; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D006801:Humans; D009431:Neural Conduction / Q000187:drug effects* / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology
D004967:Estrogens; D011960:Receptors, Estrogen; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol
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