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Allopregnanolone induces LHRH and glutamate release through NMDA receptor modulation

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Abstract

LHRH release from hypothalamus is influenced by the neurotransmitter glutamate that acts, among others, on NMDA receptors present in LHRH neurons. On the other hand, the neurosteroid allopregnanolone can modulate the activity of specific neurotransmitter receptors and affect neurotransmitter release. We examined the role of allopregnanolone on in vitro LHRH and glutamate release from mediobasal hypothalamus and anterior preoptic area of ovariectomized rats with estrogen and progesterone replacement. Moreover, we evaluated whether the neurosteroid might act through modulation of NMDA receptors. Allopregnanolone induced an increase in LHRH release. This effect was reversed when the NMDA receptors were blocked by the NMDA antagonist 2-amino-7-phosphonoheptanoic acid (AP-7) indicating that this neurosteroid would interact with NMDA receptors. Moreover allopregnanolone induced an augment in K+ evoked [3H]-glutamate release from mediobasal hypothalamus-anterior preoptic area explants and this effect was also reversed when NMDA receptors were blocked with AP-7. These results suggest an important physiologic function of allopregnanolone on the regulation of neuroendocrine function in female adult rats. Not only appears to be involved in enhancing LHRH release through modulation of NMDA receptors but also in the release of glutamate which is critical in the control of LHRH release.

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Acknowledgments

We thank Mr Jorge González (IMBECU-CONICET) for his technical assistance and Dr Zulema Sosa (National University of San Luis, Argentina) for her collaboration in preparing this manuscript. This study was financially supported by grants of Nacional Research Council of Argentina (CONICET, PIP 5942), the National University of Cuyo (SECTYP, 06/J288), and University of Mendoza (Grant 113/07).

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Authors and Affiliations

  1. Instituto de Investigaciones Biomédicas, Universidad de Mendoza, IMBECU-CONICET, Paseo Dr. Emilio Descotte 720, 5500, Mendoza, Argentina

    Fernando A. Giuliani, Roberto Yunes, Myriam Laconi & Ricardo Cabrera

  2. Laboratorio de Neuroendocrinología, Centro de Estudios Farmacológicos y Botánicos, CEFyBO-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    Claudia E. Mohn & Valeria Rettori

  3. Área de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina

    Roberto Yunes

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  1. Fernando A. Giuliani
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  2. Roberto Yunes
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  6. Ricardo Cabrera
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Correspondence to Ricardo Cabrera.

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Giuliani, F.A., Yunes, R., Mohn, C.E. et al. Allopregnanolone induces LHRH and glutamate release through NMDA receptor modulation. Endocrine 40, 21–26 (2011). https://doi.org/10.1007/s12020-011-9451-8

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  • DOI: https://doi.org/10.1007/s12020-011-9451-8

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