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Title: Effects of sex steroids on ovarian granulosa cell function
Author: Turner, Ian Matthew
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1992
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The studies described in this thesis were concerned with the role of sex steroids in the control of the differentiation of ovarian granulosa cells. This process is driven by FSH, but is subject to the influence of locally produced factors which are thought to be critical of determining the fate of a follicle. Androgens and oestrogens were known to augment the action of FSH on granulosa cell steroidogenesis, with androgens being the more potent. However, little was known about their mechanism of action, or their effects at the level of gene expression and protein synthesis. Therefore, a rat granulosa cell model was modified and validated to study the role of sex steroids in the control of expression of structurally and functionally important granulosa cell proteins and genes during FSH-stimulated differentiation. It was found that FSH caused marked changes in the synthesis of a number of prominent cellular and secreted proteins in vitro, one of which was identified by immunoprecipitation as vinculin, a cytoskeletal protein, and another as fibronectin, an extracellular matrix protein. Synthesis of both these proteins was reduced in response to FSH. The expression of mRNA encoding another cytoskeletal protein actin, was also found to be reduced by FSH treatment in vitro. All of these effects of FSH, which are consistent with observed changes in morphology during granulose cell differentiation in vitro, were strongly augmented by oestrogen and androgen. However, FSH was found to be without effect on actin mRNA levels in vivo. It was concluded that the changes in morphology reflected in these results are probably an artefact of the in vitro approach, and so do not provide a suitable model for the study of the role of steroids in ovarian physiology. A novel aspect of granulosa cell function which was thought to accompany their differentiation was production of inhibin. Little was known about the control of granulosa cell inhibin production, and so the effects of gonadotrophins and steroids on the expression of mRNA encoding the three inhibin subunits were investigated. FSH stimulated expression of mRNA encoding all three inhibin subunits in rat granulosa cells in vivo and in vitro. When administered after treatment with FSH, hCG suppressed levels of inhibin subunit mRNA. The relationship between inhibin gene expression and expression of other correlates of granulosa cell differentiation was studied in order to provide a context for these results.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available