Colocalization of estrogen receptor alpha and NMDA-2D mRNAs in amygdaloid and hypothalamic nuclei of the mouse brain.
Interactions between gonadal steroid hormones and glutamatergic neurons participate in limbic and hypothalamic functions. Glutamate receptors are divided into metabotropic and ionotropic receptors. Among ionotropic receptors, N-methyl-D-aspartate (NMDA) is involved in a variety of neurophysiological processes. In turn, NMDA receptors are composed of subunits from two families: NR1 and NR2. Recently, molecular studies have shown that the expression of NMDA-2D receptor is regulated by estrogen. Although the expression patterns of NMDA-2D and ERalpha in the rodent brain appear to overlap, it remained to be determined whether or not these two receptors co-exist, in vivo, at the level of single neurons. To test the hypothesis that NMDA-2D and ERalpha messenger ribonucleic acid (mRNA) are co-expressed in the same neurons of the adult mouse brain, we used a dual-label in situ hybridization technique. Neuronal populations were identified with digoxigenin-tagged complementary RNA probes for NMDA-2D and 35S-labeled cRNA probes for ERalpha. Our results demonstrate that a majority of the ERalpha-positive neurons also express NMDA-2D mRNA. Quantitative examination of the cellular expression in the ventromedial and arcuate nuclei of the hypothalamus (VMH and Arc) showed that 52.5% and 61.5%, respectively, of the neurons endowed with ERalpha mRNA also contain NMDA-2D mRNA. In the amygdala, 51% of ERalpha-positive cells also contain NMDA-2D mRNA. These findings provide the first anatomical evidence that ER and NMDA-2D receptors can be found in the same hypothalamic and amygdaloid neurons. Co-expression of ERalpha and NMDA-2D receptors supports the hypothesis of the interactions between glutamate receptors and estrogens in brain regions where estrogens control female reproductive behaviors and neuroendocrine functions.
The Rockefeller University, Laboratory of Neurobiology and Behavior, Box 275, 1230 York Avenue, New York, NY 10021, USA.
Hosein K
HK
Kia
Genvieve
G
Yen
Christopher J
CJ
Krebs
Donald W
DW
Pfaff
D000679:Amygdala / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D047628:Estrogen Receptor alpha; D004967:Estrogens; C464436:NR2D NMDA receptor; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid