Show simple item record

dc.contributor.advisorGore, Andrea C., 1964-en
dc.creatorMaffucci, Jacqueline Annen
dc.date.accessioned2012-10-05T14:25:56Zen
dc.date.available2012-10-05T14:25:56Zen
dc.date.issued2008-12en
dc.identifier.urihttp://hdl.handle.net/2152/18180en
dc.descriptiontexten
dc.description.abstractReproductive senescence in females is a natural part of the aging process. However, the process by which it occurs, and the relative role of each level of the hypothalamic-pituitary-gonadal axis, remains largely unknown. The neural circuitry regulating the hypothalamic axis, including glutamate acting through N-Methyl-D-Aspartate receptors (NMDARs) on GnRH neurons, appears to be key to this process. The NMDAR is tetrameric and composed of an obligatory NR1 subunit together with NR2 subunits. The subunit composition determines the channel kinetics of the receptor and changes through the life span. This dissertation examines the physiological role of the NR2b subunit on LH pulsatile release and LH surge, both important for reproductive function. The expression of NR2b subunits in the anteroventral periventricular (AVPV) nucleus of the hypothalamus was also examined in aging rats. Experiment 1 showed that the NR2b-antagonist, ifenprodil, enhanced pulsatile LH release in estradioltreated females (both age groups). Experiment 2 showed that the LH surge in middle-aged animals was slightly accelerated and that results were dependent upon prior reproductive status of the animals. In Experiment 3, examination of the NR2b-immunoreactive cell population in young, middle-aged, and aged ovariectomized females given vehicle, estradiol, or estradiol with progesterone showed an age-associated decline in NR2b density. However, the immunofluorescent fraction volume of NR1 colocalized with NR2b increased with aging, and that of immunofluorescent fraction volume of NR2b increased with estradiol treatment. This is indicative of the amount of protein expressed in the AVPV. In total, NR2b cell density in the AVPV declines with age, but the amount of NR2b expressed in NR1-positive cells increases, suggesting a larger population of NR2b containing channels. This may translate to age-associated inhibition of GnRH/LH activity, which is relieved with blockade of NR2bcontaining NMDARs. Thus, this dissertation describes a novel way to examine the mechanism by which age-associated changes to neuromodulators of the HPG axis may affect the onset of reproductive senescence.en
dc.format.mediumelectronicen
dc.language.isoengen
dc.rightsCopyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.en
dc.subject.lcshMethyl aspartate--Physiological effecten
dc.subject.lcshMethyl aspartate--Receptorsen
dc.subject.lcshLuteinizing hormone releasing hormoneen
dc.subject.lcshHypothalamus--Physiologyen
dc.subject.lcshReproduction--Endocrine aspectsen
dc.titleThe role of the N-methyl-D-aspartate receptor (NMDAR)--NR2b subunit in female reproductive agingen
dc.description.departmentNeuroscienceen
thesis.degree.departmentNeuroscienceen
thesis.degree.disciplineNeuroscienceen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record