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Steroid Regulation of GnRH Neurons
Author(s) -
MOENTER SUZANNE M.,
DEFAZIO R ANTHONY,
STRAUME MARTIN,
NUNEMAKER CRAIG S.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1286.014
Subject(s) - medicine , endocrinology , rhythm , inhibitory postsynaptic potential , neuron , patch clamp , extracellular , gonadotropin releasing hormone , period (music) , negative feedback , potassium channel , chemistry , hormone , estrogen , biology , neuroscience , electrophysiology , luteinizing hormone , microbiology and biotechnology , physics , quantum mechanics , voltage , acoustics
A bstract : GnRH neurons form the final common pathway for regulating fertility. Estradiol feedback controls GnRH release, but the cellular mechanisms are unknown. Targeted extracellular recordings were used to examine the firing rate of GFP‐identified GnRH neurons in a model for estradiol negative feedback (OVX vs. OVX+E). Episodes of increased firing rate occurred in both groups with intervals consistent with hormone secretion; estradiol more than doubled this interval. Spectral analysis identified additional rhythmic activity that was grouped by period: bursts (<100 s), clusters (100–1000 s), or episodes (>1000 s). Bursts were trains of action currents. Estradiol did not alter burst characteristics, but rather changed the patterning of inter‐burst intervals to increase the period of the low‐frequency episode rhythm. To change interburst‐interval, estradiol might alter conductances in GnRH neurons, such as potassium currents. Whole‐cell voltage‐clamp revealed that estradiol affected the amplitude, decay time, and the voltage dependence of A‐type potassium currents in GnRH neurons. Blockade of protein kinases reversed some but not all effects of estradiol. Consistent with changes in the A‐current, estradiol increased excitability in GnRH neurons. Estradiol thus targets multiple mechanisms to alter GnRH neuron firing patterns, and the balance of stimulatory and inhibitory actions determines whether the integrated response is to increase or to decrease release.