The neuroactive steroid pregnenolone sulfate stimulates the release of gonadotropin-releasing hormone from GT1-7 hypothalamic neurons, through N-methyl-D-aspartate receptors

Endocrinology
Martine El-EtrMichael Schumacher

Abstract

Immortalized hypothalamic GT1-7 neurons represent a good model system to investigate the control of GnRH secretion. Using these cells, we observed that the neuroactive steroid, pregnenolone sulfate (PREGS), is able to stimulate the release of GnRH in a dose-dependent manner through N-methyl-D-aspartate (NMDA) receptors, because its action is completely blocked by a specific NMDA receptor antagonist and magnesium. GT1-7 neurons express mRNAs for various mouse NMDA receptor subunits (zeta,1, epsilon3, epsilon4, and epsilon2, corresponding to the NR1, NR2C, NR2D, and NR2B rat subunits) and increase their spontaneous release of GnRH when incubated in the presence of exogenous glutamate or NMDA. In addition, we found that these neurons are able to release and synthesize glutamate, as demonstrated by the presence of glutamate accumulated in the defined incubation medium of the neurons, during the experiment and the expression of mRNA coding for vesicular glutamate transporter 2, a specific marker of glutamatergic neurons. The potentiating effect of PREGS on the secretion of GnRH induced by glutamate is consistent with the role of the steroid as a positive allosteric modulator of NMDA receptors. Together these results point to a novel...Continue Reading

Citations

Nov 13, 2010·PloS One·Mayumi SugimotoYoshikazu Sugimoto
Oct 27, 2009·Progress in Neurobiology·Kjell FuxeLuigi Agnati
Dec 11, 2007·Neurochemistry International·Michael SchumacherEtienne-Emile Baulieu
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Jun 28, 2016·The Journal of Physiological Sciences : JPS·Yuki AraiHitoshi Ozawa
Jun 17, 2016·Journal of Neuroendocrinology·M F RossettiR Cabrera
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Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity

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