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Genistein Excitation of Gonadotrophin‐Releasing Hormone Neurones in Juvenile Female Mice
Author(s) -
Bhattarai J. P.,
Ábrahám I. M.,
Han S. K.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12020
Subject(s) - genistein , endocrinology , medicine , kisspeptin , patch clamp , chemistry , depolarization , biology , tetrodotoxin , receptor , hormone
We investigated the effects of the phytoestrogen genistein on gonadotrophin‐releasing hormone (Gn RH ) neurones using single‐cell electrophysiology on Gn RH ‐green fluorescent protein ( GFP ) transgenic juvenile female mice. Perforated patch‐clamp recordings from Gn RH‐GFP neurones showed that approximately 83% of Gn RH neurones responded to 30 μ m genistein with a markedly prolonged membrane depolarisation. This effect not only persisted in the presence of tetrodotoxin, but also in the presence of amino acid receptor antagonists, indicating the direct site of action on postsynaptic Gn RH neurones. Using a voltage clamp technique, we found that 30 μ m genistein increased the frequency of synaptic current of Gn RH neurones clamped at −60 mV in the presence of glutamate receptor blocker but not GABA A receptor blocker. Pre‐incubation of Gn RH neurones with 30 μ m genistein enhanced kisspeptin‐induced membrane depolarisation and firing. Gn RH neurones of juvenile mice injected with genistein in vivo showed an enhanced kisspeptin response compared to vehicle‐injected controls. The transient receptor potential channel (TRPC) blocker 2‐aminoethoxydiphenyl borate (75 μ m ) blocked the genistein‐mediated response on Gn RH neurones. These results demonstrate that genistein acts on Gn RH neurones in juvenile female mice to induce excitation via GABA neurotransmission and TRPCs to enhance kisspeptin‐induced activation.