Estradiol (E2) stimulates luteinizing hormone-releasing hormone (LHRH) synthesis and release from neurons in the preoptic area (POA). Stimulatory effects of E2 on LHRH neurons are critical for preovulatory surge of luteinizing hormone (LH). The neural mechanisms mediating these events are unclear. Glutamate and γ-aminobutyric acid (GABA), the most prevalent excitatory and inhibitory neurotransmitters in the brain, play important roles in the regulation of LHRH neurons. Activation of the N-methyl, D-aspartate (NMDA) subtype glutamate receptor is required for E2-dependent LHRH and LH surge release. It is unknown whether these actions are direct or relayed indirectly via other systems. NMDA treatment induces increases in LHRH mRNA levels, but it is unclear whether NMDA receptor activation mediates E2-dependent increases LHRH gene expression on the day of the LH surge. Dual-label in situ hybridization histochemistry (ISHH) and pharmacological techniques revealed a subpopulation of LHRH neurons in midline POA nuclei preferentially contains NMDAR1 and NMDAR2 receptor mRNAs and responds preferentially to NMDA with increased LHRH mRNA. Results show NMDA receptor activation is not required for E2-induced increases LHRH mRNA on the day of the LH surge. GABA mediates inhibitory effects on LHRH neurons. GABAergic inhibition must be relieved before LHRH and LH surge release can occur. Evidence indicates neurons in the anteroventral periventricular nucleus (AVPV), a region important in E2-dependent LHRH neural regulation, exhibit a mixed GABAergic/glutamatergic phenotype. Using dual-label ISHH, I showed that vesicular glutamate transporter 2 (VGLUT2) and glutamic acid decarboxylase 65 and 67 mRNAs are colocalized AVPV neurons and in other brain regions. Results demonstrate GABAergic/glutamatergic AVPV neurons in females are more numerous and greater percentages contain estrogen receptor mRNAs than males. Using immunocytochemistry and confocal microscopy, I showed that E2 increases VGLUT2 levels and decreases vesicular GABA transporter levels in double-labeled terminals contacting medial LHRH neurons. Results indicate that medial LHRH neurons are regulated uniquely by preferential expression of NMDA receptors and by dynamic E2-dependent changes in inhibitory and excitatory input from “dual-function” neurons on the day of the LH surge. Results also reveal sexual dimorphisms in AVPV GABAergic/glutamatergic neurons, which may explain the absence of LH surges in males.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:dissertations-3890 |
| Date | 01 January 2004 |
| Creators | Ottem, Erich Norse |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Language | English |
| Detected Language | English |
| Type | text |
| Source | Doctoral Dissertations Available from Proquest |
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