TY - JOUR
T1 - α-Adrenergic receptor antagonism and N-methyl-D-aspartate (NMDA) induced luteinizing hormone release in female rhesus macaques
AU - Urbanski, Henryk F.
AU - Garyfallou, Vasilios T.
AU - Kohama, Steven G.
AU - Hess, David L.
N1 - Funding Information:
We wish to thank Sherri Falls, Kevin Grund, Rick Jones, and Ty May for help in caring for the animals, Bill Baughman for surgical assistance, and Evida Katayama for technical assistance with the hormone assays. We are also grateful to Dr. K. Moriyoshi (Kyoto University, Japan) for providing us with the NMDAR1 cDNA clone. Preliminary findings from these studies were reported at the 28th Annual Meeting of the Society for the Study of Reproduction, Davis, CA, 1995 [38] . This research was supported by grants from the National Institutes of Health (HD-29186, HD-24312, HD-18185 and RR-00163). ORPRC publication number 2015.
PY - 1997/1/2
Y1 - 1997/1/2
N2 - The stimulatory influence of N-methyl-D-aspartate (NMDA), a glutamate receptor agonist, on LH secretion is well established in several mammalian species including the rhesus macaque. Although the mechanism of excitation appears to involve enhanced GnRH secretion, it is unclear whether the GnRH neurons respond directly to this excitation or whether stimulatory inter-neurons are involved. This study investigated the possibility that noradrenergic afferents play a major role in mediating the response of the primate hypothalamo-pituitary reproductive axis to NMDA. In situ hybridization histochemistry, using a cRNA probe coding for the NMDAR1 receptor subunit, revealed abundant mRNA in the locus coeruleus, a brain area rich in noradrenergic neurons. Furthermore, using double-label fluorescence immunocytochemistry, the tyrosine hydroxylase immunopositive neurons of the locus coeruleus showed immunoreactivity for the NMDAR1 receptor subunit protein. A second experiment examined whether prazosin, an α-adrenergic receptor antagonist, could attenuate NMDA-induced stimulation of LH release. Prazosin (either 1 or 5 mg/kg b.wt., i.v.) was administered to female rhesus macaques during the luteal phase of the menstrual cycle, 40 min before administration of NMDA (10 mg/kg b.wt., i.v.). Regardless of the prazosin pre-treatment, plasma LH concentrations showed a significant increase (P < 0.01) within 10 min of the administration of NMDA. Therefore, in spite of the evidence that at least some of the noradrenergic neurons of the primate hindbrain express the NMDAR1 receptor subunit, it is unlikely that noradrenergic inter-neuronal pathways alone play a major role in mediating the stimulators action of NMDA on GnRH/LH secretion in primates. Indeed, because the GNRH neurons of the rhesus macaque are located diffusely in various regions of the hypothalamus and medial-septal/preoptic area, their net response to excitatory amino acids is likely to be more complicated, involving a combination of both stimulatory and inhibitory inter-neurons, and possibly also a direct interaction.
AB - The stimulatory influence of N-methyl-D-aspartate (NMDA), a glutamate receptor agonist, on LH secretion is well established in several mammalian species including the rhesus macaque. Although the mechanism of excitation appears to involve enhanced GnRH secretion, it is unclear whether the GnRH neurons respond directly to this excitation or whether stimulatory inter-neurons are involved. This study investigated the possibility that noradrenergic afferents play a major role in mediating the response of the primate hypothalamo-pituitary reproductive axis to NMDA. In situ hybridization histochemistry, using a cRNA probe coding for the NMDAR1 receptor subunit, revealed abundant mRNA in the locus coeruleus, a brain area rich in noradrenergic neurons. Furthermore, using double-label fluorescence immunocytochemistry, the tyrosine hydroxylase immunopositive neurons of the locus coeruleus showed immunoreactivity for the NMDAR1 receptor subunit protein. A second experiment examined whether prazosin, an α-adrenergic receptor antagonist, could attenuate NMDA-induced stimulation of LH release. Prazosin (either 1 or 5 mg/kg b.wt., i.v.) was administered to female rhesus macaques during the luteal phase of the menstrual cycle, 40 min before administration of NMDA (10 mg/kg b.wt., i.v.). Regardless of the prazosin pre-treatment, plasma LH concentrations showed a significant increase (P < 0.01) within 10 min of the administration of NMDA. Therefore, in spite of the evidence that at least some of the noradrenergic neurons of the primate hindbrain express the NMDAR1 receptor subunit, it is unlikely that noradrenergic inter-neuronal pathways alone play a major role in mediating the stimulators action of NMDA on GnRH/LH secretion in primates. Indeed, because the GNRH neurons of the rhesus macaque are located diffusely in various regions of the hypothalamus and medial-septal/preoptic area, their net response to excitatory amino acids is likely to be more complicated, involving a combination of both stimulatory and inhibitory inter-neurons, and possibly also a direct interaction.
KW - GnRH
KW - glutamate
KW - idazoxan
KW - locus coeruleus
KW - prazosin
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U2 - 10.1016/S0006-8993(96)01083-9
DO - 10.1016/S0006-8993(96)01083-9
M3 - Article
C2 - 9030417
AN - SCOPUS:0031016369
SN - 0006-8993
VL - 744
SP - 96
EP - 104
JO - Brain research
JF - Brain research
IS - 1
ER -