Pulsatile @entity1176 release is required for fertility and is regulated by @entity134 feedback. Whether or not @entity230 or their metabolites act directly on GnRH neurons is not well established. In some neurons, @entity134 metabolites known as neurosteroids modulate the function of the @entity8771 receptor. Specifically, the @entity1420 derivative @entity7997 is an allosteric agonist at this receptor, whereas the @entity342 @entity9027 ( @entity2990 ) is an allosteric antagonist. We hypothesized these metabolites act similarly on GnRH neurons to modify the response to @entity1246 . Whole-cell voltage-clamp recordings of GABAergic miniature postsynaptic currents (mPSCs) were made from green fluorescent protein-identified GnRH neurons in brain slices from diestrous @entity19 . Glutamatergic currents were blocked with antagonists and action potentials blocked with @entity1022 , minimizing presynaptic effects of treatments. @entity7997 (5 microm) increased mPSC rate of rise, amplitude and decay time by 15.9 +/- 6.1%, 16.5 +/- 6.3%, and 58.3 +/- 18.6%, respectively (n = 7 cells). DHEAS (5 microm) reduced mPSC rate of rise (32.1 +/- 5.7%) and amplitude (27.6 +/- 4.3%) but did not alter decay time (n = 8). Effects of both neurosteroids were dose dependent between 0.1 and 10 microm. In addition to independent actions, DHEAS also reversed effects of @entity7997 on rate of rise and amplitude so that these parameters were returned to pretreatment baseline values (n = 6). These data indicate @entity7997 increases and DHEAS decreases responsiveness of GnRH neurons to activation of @entity8771 receptors by differentially modulating current flow through @entity8771 receptor @entity2865 channels. This provides one mechanism for direct @entity134 feedback to GnRH neurons.

Neurosteroids alter XXXX postsynaptic currents in gonadotropin-releasing hormone neurons: a possible mechanism for direct steroidal control.

@entity1246 :: ('MESH:D005680', 'Chemical') :: ['GABA'] @entity1420 :: ('MESH:D011374', 'Chemical') :: ['progesterone'] @entity2990 :: ('CHEBI:16814', 'Chemical') :: ['DHEAS'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity2865 :: ('CHEBI:17996', 'Chemical') :: ['chloride'] @entity1022 :: ('MESH:D013779', 'Chemical') :: ['tetrodotoxin'] @entity134 :: ('CHEBI:35341', 'Chemical') :: ['steroid'] @entity7997 :: ('MESH:D011280', 'Chemical') :: ['Allopregnanolone', 'allopregnanolone'] @entity342 :: ('CHEBI:50113', 'Chemical') :: ['androgen'] @entity1176 :: ('MESH:D007987', 'Chemical') :: ['GnRH'] @entity9027 :: ('MESH:D019314', 'Chemical') :: ['dehydroepiandrosterone sulfate'] @entity230 :: ('MESH:D013256', 'Chemical') :: ['steroids'] @entity8771 :: ('14405(Tax:10090)', 'Gene') :: ['GABAA']
@entity1246 :: (MESH:D005680,Chemical) :: ['gamma-aminobutyric acid']
