| dc.identifier.uri | http://hdl.handle.net/11401/76539 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Kisspeptin neurons are potent regulators of gonadotropin-releasing hormone (GnRH) neurons, necessary for pubertal development and adult reproductive competence. Estradiol (E<sub>2</sub>) and testosterone (T), along with peripheral metabolic signals, such as leptin and insulin, regulate GnRH release indirectly, in part through the activation or inhibition of kisspeptin neurons. The changes in GnRH release and consequently in gonadotropin levels caused by these peripheral signals are strongly linked to changes in hypothalamic kisspeptin (<italic>Kiss1</italic>) gene expression. However, little is known about the intracellular signaling pathways that regulate <italic>Kiss1</italic>. The phospholipid enzyme phosphoinositide 3-kinase (PI3K) is a major downstream effector of steroid hormones and metabolic cues. We hypothesize that PI3K in kisspeptin neurons integrates peripheral signals to regulate <italic>Kiss1</italic> expression, thus altering GnRH release. To test our hypothesis, we used transgenic mice and Cre-LoxP technology to delete PI3K catalytic subunits, p110α and p110β , in kisspeptin cells (Kiss-p110α /β KO). Ablation of PI3K from kisspeptin neurons did not alter overall pubertal development in either male or female mice. In adult animals, LH levels were lower in Kiss-p110α /β KO male mice regardless of gonadal status when compared to wild type. However, basal LH levels in Kiss-p110α /β KO female mice were not significantly different from wild type. We also examined <italic>Kiss1</italic> mRNA expression among groups of gonad-intact, gonadectomized (GDX), and GDX + steroid-replaced mice. Compared to wild type, <italic>Kiss1</italic> cell number was lower in the anteroventral periventricular nucleus (AVPV) of intact Kiss-p110α /β KO males. In the arcuate (ARC) nucleus KO males showed lower <italic>Kiss1</italic> cell numbers regardless of gonadal status. A significant genotype effect was observed in the ARC of females from the GDX group, but not in the intact or in the E<sub>2</sub>-replaced group. In addition, compared to wild type, a substantial reduction in kisspeptin immunoreactivity was observed in the ARC of intact adult Kiss-p110α /β KO males and females. Our data supports a key role of PI3K signaling in the regulation of <italic>Kiss1</italic> expression in both sexes and LH levels in males. These studies have the potential to identify novel therapeutic targets to treat reproductive disorders of unknown etiology. | |
| dcterms.available | 2017-09-20T16:50:36Z | |
| dcterms.contributor | Acosta-Martinez, Maricedes | en_US |
| dcterms.contributor | Kritzer, Mary | en_US |
| dcterms.contributor | Shelly, Maya | en_US |
| dcterms.contributor | White, Thomas | en_US |
| dcterms.contributor | El-Maghrabi, Raafat. | en_US |
| dcterms.creator | Beymer, Matthew John Alan | |
| dcterms.dateAccepted | 2017-09-20T16:50:36Z | |
| dcterms.dateSubmitted | 2017-09-20T16:50:36Z | |
| dcterms.description | Department of Molecular Genetics and Microbiology. | en_US |
| dcterms.extent | 103 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/76539 | |
| dcterms.issued | 2014-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:50:36Z (GMT). No. of bitstreams: 1
Beymer_grad.sunysb_0771E_11786.pdf: 19649202 bytes, checksum: e2f285bfd3b49fb9cf775696f43bbd0e (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Biology | |
| dcterms.subject | Kisspeptin, Phosphoinositide 3-Kinase, Reproductive Physiology | |
| dcterms.title | The Role of Phosphoinositide 3-Kinase in Regulating Kisspeptin Neurons within the Hypothalamic-Pituitary-Gonadal Axis | |
| dcterms.type | Dissertation | |
