Persistent Link:
http://hdl.handle.net/10150/284259
Title:
Gonadal steroids, reproductive aging and the primate hypothalamus
Author:
Abel, Ty William
Issue Date:
1999
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:
The gonadal steroid withdrawal of menopause is associated with neuronal hypertrophy and increased tachykinin gene expression in the hypothalamic infundibular nucleus. Previous studies have shown that secretion of hypothalamic b -endorphin is modified by gonadal steroids, and there are consistent age-related changes in b -endorphin neurons in rodents. Therefore, in situ hybridization was used to determine if the expression of POMC mRNA, the precursor for b -endorphin, is altered in the hypothalamus of postmenopausal women. The number of POMC mRNA-containing neurons/section in the infundibular nucleus was reduced by 65% in postmenopausal women. In contrast, there was no significant difference in the number of neurons expressing POMC gene transcripts in the retrochiasmatic region. Our findings support the hypothesis that the activity of hypothalamic POMC neurons is decreased in the infundibular nucleus of postmenopausal women. In a second study, we examined the effects of hormone replacement therapy (HRT) on the hypothalamus of young, ovariectomized cynomolgus monkeys. HRT dramatically suppressed tachykinin gene expression while having no detectable effects on POMC neurons. These results provide strong support for the hypothesis that alterations in tachykinin neurons in postmenopausal women are secondary to estrogen withdrawal. Conversely, postmenopausal changes in POMC gene expression may reflect hypothalamic aging. Finally, we found no evidence that HRT, in doses designed to mimic currently prescribed regimens, produces signs of estrogen toxicity in the primate infundibular nucleus. Degenerative changes, including neuron loss, have been reported in the arcuate nucleus of aging rodents, and hypothalamic aging has been shown to contribute to reproductive decline in these species. In addition, in the infundibular nucleus of postmenopausal women, there is an age-associated decline in proopiomelanocortin gene expression. To evaluate the possibility of neuron loss associated with reproductive aging, unbiased stereological methods were used to compare the total number of infundibular neurons between groups of premenopausal and postmenopausal women. The mean neuronal volume was increased by 40% in postmenopausal women but there was no change in the total number of neurons. These data suggest that the neuronal hypertrophy observed in the postmenopausal human hypothalamus is not a pathological process secondary to degeneration of adjacent infundibular neurons.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Anatomy.; Biology, Neuroscience.; Gerontology.; Biology, Animal Physiology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Neurosciences
Degree Grantor:
University of Arizona
Advisor:
Rance, Naomi

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleGonadal steroids, reproductive aging and the primate hypothalamusen_US
dc.creatorAbel, Ty Williamen_US
dc.contributor.authorAbel, Ty Williamen_US
dc.date.issued1999en_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.abstractThe gonadal steroid withdrawal of menopause is associated with neuronal hypertrophy and increased tachykinin gene expression in the hypothalamic infundibular nucleus. Previous studies have shown that secretion of hypothalamic b -endorphin is modified by gonadal steroids, and there are consistent age-related changes in b -endorphin neurons in rodents. Therefore, in situ hybridization was used to determine if the expression of POMC mRNA, the precursor for b -endorphin, is altered in the hypothalamus of postmenopausal women. The number of POMC mRNA-containing neurons/section in the infundibular nucleus was reduced by 65% in postmenopausal women. In contrast, there was no significant difference in the number of neurons expressing POMC gene transcripts in the retrochiasmatic region. Our findings support the hypothesis that the activity of hypothalamic POMC neurons is decreased in the infundibular nucleus of postmenopausal women. In a second study, we examined the effects of hormone replacement therapy (HRT) on the hypothalamus of young, ovariectomized cynomolgus monkeys. HRT dramatically suppressed tachykinin gene expression while having no detectable effects on POMC neurons. These results provide strong support for the hypothesis that alterations in tachykinin neurons in postmenopausal women are secondary to estrogen withdrawal. Conversely, postmenopausal changes in POMC gene expression may reflect hypothalamic aging. Finally, we found no evidence that HRT, in doses designed to mimic currently prescribed regimens, produces signs of estrogen toxicity in the primate infundibular nucleus. Degenerative changes, including neuron loss, have been reported in the arcuate nucleus of aging rodents, and hypothalamic aging has been shown to contribute to reproductive decline in these species. In addition, in the infundibular nucleus of postmenopausal women, there is an age-associated decline in proopiomelanocortin gene expression. To evaluate the possibility of neuron loss associated with reproductive aging, unbiased stereological methods were used to compare the total number of infundibular neurons between groups of premenopausal and postmenopausal women. The mean neuronal volume was increased by 40% in postmenopausal women but there was no change in the total number of neurons. These data suggest that the neuronal hypertrophy observed in the postmenopausal human hypothalamus is not a pathological process secondary to degeneration of adjacent infundibular neurons.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Anatomy.en_US
dc.subjectBiology, Neuroscience.en_US
dc.subjectGerontology.en_US
dc.subjectBiology, Animal Physiology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineNeurosciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorRance, Naomien_US
dc.identifier.proquest9927501en_US
dc.identifier.bibrecord.b39569305en_US
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