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Novel hypothalamic G protein-coupled receptors involved in the control of reproduction
Dissertation (MSc (Medical Immunology))--University of Pretoria, 2018.
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| Format: | Thesis |
| Language: | English |
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2026
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| _version_ | 1867613446280839168 |
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| access_status_str | Open Access |
| author2 | Newton, Claire |
| author_browse | Newton, Claire |
| author_facet | Newton, Claire |
| collection | Thesis |
| description | Dissertation (MSc (Medical Immunology))--University of Pretoria, 2018. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/110107 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:36:14.878Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/110107 Novel hypothalamic G protein-coupled receptors involved in the control of reproduction Newton, Claire eauger@icon.co.za Anderson, Ronald Millar, Robert Peter Auger, Genevieve Marie Reproductive dysfunctions oxytocin receptor Y4 neuropeptide Y receptor Dissertation (MSc (Medical Immunology))--University of Pretoria, 2018. In the hypothalamus, various G-protein coupled receptors (GPCRs) form part of the regulatory pathways of the hypothalamus-pituitary-gonadal (HPG) axis. The master hormone regulator of the HPG axis is the gonadotropin-releasing hormone (GnRH). Defects in GnRH neuron activity are associated with reproductive dysfunctions including normosmic congenital hypogonadotropic hypogonadism (nCHH) and Kallmann syndrome (KS). DNA from a cohort of European nCHH/KS patients was exome sequenced. Mutations in GPCR genes were identified and two hypothalamic GPCRs of interest were identified; oxytocin receptor (OXTR) and Y4 neuropeptide Y receptor (NPY4R). Both receptors have been shown to have a role in reproduction, however, mutations in neither have been previously implicated in causing KS/nCHH respectively. The aim was to determine whether identified mutations in the receptors affected their functionality and may therefore potentially be causative to the reproductive dysfunctions. Using six different online tools, the compound heterozygous (L282V+E339K) mutation identified in OXTR and the double heterozygous (V40M/L287P) mutation identified in NPY4R were examined for prediction of deleterious effects. These mutant GPCRs were then cloned into a mammalian N-terminal epitope-tagging expression vector. A receptor ELISA assay and receptor signalling assay were utilized to compare wild-type (WT) and mutant receptor cell surface expression and functionality in vitro. 2/6 bioinformatic tools predicted the L282V mutation would be deleterious and 3/6 predicted that the E339K mutation would be deleterious. The in vitro results indicated a significant decrease (p Medical Immunology MSc (Medical Immunology) 2026-05-15T17:26:18Z 2026-05-15T17:26:18Z 18/05/07 2018 Dissertation http://hdl.handle.net/2263/110107 en application/pdf |
| spellingShingle | Reproductive dysfunctions oxytocin receptor Y4 neuropeptide Y receptor Novel hypothalamic G protein-coupled receptors involved in the control of reproduction |
| title | Novel hypothalamic G protein-coupled receptors involved in the control of reproduction |
| title_full | Novel hypothalamic G protein-coupled receptors involved in the control of reproduction |
| title_fullStr | Novel hypothalamic G protein-coupled receptors involved in the control of reproduction |
| title_full_unstemmed | Novel hypothalamic G protein-coupled receptors involved in the control of reproduction |
| title_short | Novel hypothalamic G protein-coupled receptors involved in the control of reproduction |
| title_sort | novel hypothalamic g protein coupled receptors involved in the control of reproduction |
| topic | Reproductive dysfunctions oxytocin receptor Y4 neuropeptide Y receptor |
| url | http://hdl.handle.net/2263/110107 |