title: Allopregnanolone induces LHRH and glutamate release through NMDA receptor modulation.
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 [(3)H]-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.
authors: Instituto de Investigaciones Biomédicas, Universidad de Mendoza, IMBECU-CONICET, Paseo Dr. Emilio Descotte 720, 5500, Mendoza, Argentina.
authors: Fernando A
authors: FA
authors: Giuliani
authors: Roberto
authors: R
authors: Yunes
authors: Claudia E
authors: CE
authors: Mohn
authors: Myriam
authors: M
authors: Laconi
authors: Valeria
authors: V
authors: Rettori
authors: Ricardo
authors: R
authors: Cabrera
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015914:Estrogen Replacement Therapy; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D023421:Models, Animal; D016202:N-Methylaspartate / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010052:Ovariectomy; D011280:Pregnanolone / Q000494:pharmacology*; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D007987:Gonadotropin-Releasing Hormone; D018698:Glutamic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D011280:Pregnanolone; C031231:2-amino-7-phosphonoheptanoic acid