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dc.contributor.authorCurrie, Richard John Williamen
dc.date.accessioned2018-05-14T10:12:13Z
dc.date.available2018-05-14T10:12:13Z
dc.date.issued1994
dc.identifier.urihttp://hdl.handle.net/1842/29719
dc.description.abstracten
dc.description.abstractThe investigations detailed in this thesis were undertaken to determine the mechanisms regulating the post translational control of LH secretion in the ewe. LH is stored within dense core secretory granules in the gonadotrophs of the adenohypophysis. Studies on cellular ultrastructure and gene expression were conducted on pituitary glands obtained from Welsh mountain ewes at points throughout the oestrous cycle.en
dc.description.abstractIn order to determine if a structural priming response of gonadotrophin granules in preparation for the preovulatory LH surge was present in the sheep, fixed pituitary tissue was examined using immunogold labelling techniques under the electron microscope. In the luteal phase, 20% of gonadotrophs possessed granules located in one aspect of the cytoplasm juxtaposed to the nearest sinusoid, leading to the appearance of a polarised cell. The percentage of polarised cells increased throughout the cycle, reaching a peak of 90% in mid LH surge. Stereological analysis of granule diameter showed that exocytosis occurred in a size dependant manner. Initial secretion occurred from the 150-180nm size class with the larger granules released only during the preovulatory LH surge. LHß mRNA abundance decreased from luteal through follicular phase, reaching its lowest value during the surge. The replenishment of intracellular LH stores occurred initially via the synthesis of the smaller granule size classes, first visible in the cytoplasm 48h after an induced LH surge. As cells refilled, displaying a morphology similar to a typical luteal phase gonadotroph at 96h post surge, the diameter of granules synthesized increased, approaching values observed in the late luteal phase. Throughout the refill phase, LHß mRNA abundance did not change. These data suggest that the preovulatory LH surge, in the ewe, is not related to increased synthesis of LH but a progressive recruitment of gonadotrophs into a releasing state as indicated by the polarisation of secretory granules towards the abutting capillary. Furthermore, the absence of changes in steady state LHß mRNA suggests that post transcriptional mechanisms operate to mediate the refilling of the LH stores.en
dc.description.abstractThe polarisation of gonadotrophs was prevented by the action of a GnRH antagonist. The actions of GnRH and oestradiol, independently, were able to induce polarisation. However, the direction of the granule translocation was incorrect in some 30% of cases indicating that in vivo the two hormone actions synergise to ensure the correct direction of the granule polarisation.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2018 Block 18en
dc.relation.isreferencedbyAlready catalogueden
dc.titlePost-translational control of luteinizing hormone secretionen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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