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dc.contributor.authorLeaver, H. Anneen
dc.date.accessioned2019-02-15T14:33:05Z
dc.date.available2019-02-15T14:33:05Z
dc.date.issued1978en
dc.identifier.urihttp://hdl.handle.net/1842/34950
dc.description.abstracten
dc.description.abstractThe rat corpus luteum produces progesterone which is essential for the maintenance of pregnancy. This steroidogenesis is influenced and maintained by 'the pituitary trophic hormone luteinising hormone. However, the mechanism of the long-term and the acute activation of steroidogenesis by luteinising hormone is not known. The substrate of steroidogenesis, cholesterol, is hydroxylated by the cholesterol side chain cleavage enzyme in the mitochondria of the corpus luteum cell. This substrate cholesterol is derived either from circulating extracellular cholesterol or as a product of intracellular cholesterol ester hydrolase activity.en
dc.description.abstractThe object of the studies described was to investigate the control of steroidogenesis in relation to its substrate, cholesterol. The superovulated rat ovary was used in these studies as a model system.en
dc.description.abstractThe long-term induction of steroidogenesis by gonadotrophins in the rat corpus luteum was initially studied. The rate-limiting factor(s) in this induction processs were investigated. An activator or component of the cholesterol side chain cleavage enzyme appeared to be rate-limiting in the process of long-term activation.en
dc.description.abstractCharacteristics of cholesterol side chain cleavage were examined in an isolated mitochondrial preparation. In such a preparation substrate cholesterol was found to limit the rate of steroidogenesis and certain experiments suggested that substrate depletion also limited steroidogenesis in vivo. Therefore the interaction of cholesterol with the mitochondrial cholesterol side chain cleavage enzyme was investigated, Enzymological and spectrophotometric methods were used to study this interaction at the active site of the cholesterol side chain cleavage enzyme. These experiments showed that the access of substrate to the active site limited the rate of cholesterol side chain cleavage in mitochondria from normal and luteinising hormone- or cycloheximide-pretreated rats.en
dc.description.abstractThe supply of cholesterol to the mitochondria was studied. Cholesterol ester hydrolase enzymes in the rat corpus luteum were characterised. In addition to the previously characterised supernatant enzyme, two particulate cholesterol ester hydrolases were identified. The pH dependence of these particulate enzymes' activity suggested that one was lysosomal and one microsomal in origin.en
dc.description.abstractProperties of the process of cholesterol uptake by rat corpus luteum mitochondria were then investigated. These studies suggested that cholesterol uptake by mitochondria was not rate-limiting in steroidogenesis.en
dc.description.abstractFinally, the control of steroidogenesis by factors other than substrate availability was studied. One regulatory factor which was investigated was the protein synthesis inhibitor, cycloheximide. The effect of other inhibitors of eukaryotic protein synthesis on steroidogenesis was examined,, However, the action of the inhibitors did not resemble the effect of cycloheximide„ Attempts were made to identify the subcellular distribution of the putative rapidly turning over protein factor which has been postulated to control steroidogenesis. No stimulatory factor was identified in any subcellular fraction. These experiments suggested that cycloheximide may inhibit steroidogenesis by some mechanism which does not involve the inhibition of protein synthesis.en
dc.description.abstractThe control of steroidogenesis through alteration in the properties of the mitochondrial membrane was investigated. Mechanical disruption of the mitochondrial membrane and disruption by calcium ions increased the rate of steroidogenesis. This suggested that the control of steroidogenesis could be mediated by some effect on the mitochondrial membrane.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2019 Block 22en
dc.relation.isreferencedbyen
dc.titleSteroidogenesis and its control in rat corpus luteumen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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