Ovarian Steroid Modulation of Neuropeptide Gene Expression and Neuronal Morphology in the Primate Hypothalamus

Persistent Link:
http://hdl.handle.net/10150/194500
Title:
Ovarian Steroid Modulation of Neuropeptide Gene Expression and Neuronal Morphology in the Primate Hypothalamus
Author:
Rometo, Adonna Marie
Issue Date:
2008
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
In the United States, there are currently more than 40 million postmenopausal women. These women are faced with a variety of physiological changes including ovarian steroid withdrawal and alterations in hypothalamic neurons. Within the hypothalamic infundibular nucleus of postmenopausal women, there is neuronal hypertrophy and an increase in neurokinin B gene expression. Recent studies identified the kisspeptins and dynorphins as major regulators of reproduction. In our first experiment, we examined the location and alterations of KiSS-1 mRNA-expressing neurons in the hypothalami of pre and postmenopausal women. KiSS-1 neurons were largely confined to the infundibular nucleus, and in postmenopausal women, exhibited neuronal hypertrophy and increased gene expression. To determine if these changes could result from alterations in ovarian steroids, we investigated KiSS-1 gene expression in the hypothalamic infundibular nucleus of non-human primates. Similar to the findings in postmenopausal women, ovariectomy of monkeys resulted in neuronal hypertrophy and increased KiSS-1 gene expression within the infundibular nucleus. Further, estrogen treatment of ovariectomized monkeys yielded a dramatic decrease in KiSS-1 gene expression. Together, these findings suggest that the postmenopausal alterations in KiSS-1 neurons are secondary to ovarian failure.In a second study, we examined alterations in dynorphin gene expression in the hypothalami of pre and postmenopausal women. Dynorphin mRNA-expressing neurons were identified in multiple nuclei. Numbers of dynorphin neurons were decreased within the mPOA and infundibular nucleus of postmenopausal women. In the infundibular nucleus of postmenopausal women, dynorphin neurons were hypertrophied. To determine the contribution of ovarian steroids on dynorphin gene expression, we examined dynorphin mRNA in a monkey model of menopause. Young ovariectomized monkeys exhibited hypertrophy of dynorphin neurons, with no changes in dynorphin gene expression. Estrogen replacement yielded a decrease in neuronal size and an increase in dynorphin neuron number.In future studies, we will use Quantum Dot FISH to determine if NKB, KiSS-1, and dynorphin are colocalized in the hypertrophied neurons. These neuropeptides are involved in the regulation of GnRH and changes in their gene expression likely contribute to postmenopausal alterations in reproductive hormones. Our findings provide greater understanding of the postmenopausal condition and offer opportunities for pharmaceutical investigation and treatment.
Type:
text; Electronic Dissertation
Keywords:
Menopause; Kisspeptin; Dynorphin; GnRH; Primate
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Physiological Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Rance, Naomi E
Committee Chair:
Rance, Naomi E

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleOvarian Steroid Modulation of Neuropeptide Gene Expression and Neuronal Morphology in the Primate Hypothalamusen_US
dc.creatorRometo, Adonna Marieen_US
dc.contributor.authorRometo, Adonna Marieen_US
dc.date.issued2008en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractIn the United States, there are currently more than 40 million postmenopausal women. These women are faced with a variety of physiological changes including ovarian steroid withdrawal and alterations in hypothalamic neurons. Within the hypothalamic infundibular nucleus of postmenopausal women, there is neuronal hypertrophy and an increase in neurokinin B gene expression. Recent studies identified the kisspeptins and dynorphins as major regulators of reproduction. In our first experiment, we examined the location and alterations of KiSS-1 mRNA-expressing neurons in the hypothalami of pre and postmenopausal women. KiSS-1 neurons were largely confined to the infundibular nucleus, and in postmenopausal women, exhibited neuronal hypertrophy and increased gene expression. To determine if these changes could result from alterations in ovarian steroids, we investigated KiSS-1 gene expression in the hypothalamic infundibular nucleus of non-human primates. Similar to the findings in postmenopausal women, ovariectomy of monkeys resulted in neuronal hypertrophy and increased KiSS-1 gene expression within the infundibular nucleus. Further, estrogen treatment of ovariectomized monkeys yielded a dramatic decrease in KiSS-1 gene expression. Together, these findings suggest that the postmenopausal alterations in KiSS-1 neurons are secondary to ovarian failure.In a second study, we examined alterations in dynorphin gene expression in the hypothalami of pre and postmenopausal women. Dynorphin mRNA-expressing neurons were identified in multiple nuclei. Numbers of dynorphin neurons were decreased within the mPOA and infundibular nucleus of postmenopausal women. In the infundibular nucleus of postmenopausal women, dynorphin neurons were hypertrophied. To determine the contribution of ovarian steroids on dynorphin gene expression, we examined dynorphin mRNA in a monkey model of menopause. Young ovariectomized monkeys exhibited hypertrophy of dynorphin neurons, with no changes in dynorphin gene expression. Estrogen replacement yielded a decrease in neuronal size and an increase in dynorphin neuron number.In future studies, we will use Quantum Dot FISH to determine if NKB, KiSS-1, and dynorphin are colocalized in the hypertrophied neurons. These neuropeptides are involved in the regulation of GnRH and changes in their gene expression likely contribute to postmenopausal alterations in reproductive hormones. Our findings provide greater understanding of the postmenopausal condition and offer opportunities for pharmaceutical investigation and treatment.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectMenopauseen_US
dc.subjectKisspeptinen_US
dc.subjectDynorphinen_US
dc.subjectGnRHen_US
dc.subjectPrimateen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorRance, Naomi Een_US
dc.contributor.chairRance, Naomi Een_US
dc.contributor.committeememberHoyer, Patriciaen_US
dc.contributor.committeememberLevine, Ricken_US
dc.contributor.committeememberVanderah, Todden_US
dc.identifier.proquest2726en_US
dc.identifier.oclc659749743en_US
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