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Title: Molecular mechanisms of ovulation and luteinisation
Author: Simpson, Gillian E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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Both G and P exhibit anti-inflammatory characteristics in the uterus and since ovulation has been likened to an inflammatory reaction, it is my hypothesis that P and G work in synergy through genomic and nongenomic receptors to regulate ovulation. Therefore, RNase protection assays and in situ hybridisation were developed to examine spatio-temporal expression of genes believed to be crucial to P and G production, metabolism and reception in the rat ovary. Gonadotrophins were shown to up-regulate the expression of StAR, P450scc, 3bHSD and 11bHSD1 and down-regulate 11bHSD2 expression in whole rat ovary and in GC cultures. PR and mRNA was expressed transiently 6h after the LH surge whereas GR mRNA was expressed throughout the cycle. Therefore, genes that regulate the synthesis of P, the activation of G and both genomic receptors were developmentally regulated, being induced by gonadotrophins. In GC cultures, after priming with FSH to induce functional maturity, concurrent addition of the antiprogestin, RU486, inhibited the stimulatory effects of LH on 11bHSD1, StAR, P450scc and 3bHSD mRNA levels, 6h after treatment began. PR gene expression was unaltered. However, with 12h treatment, 11bHSD gene expression had increased and StAR, P450scc and 3bHSD mRNA levels were unchanged with RU486. The previously recognised ability of RU486 to halt ovulation and luteinisation may therefore be due to its effect on the expression of genes regulating P and G. However, nongenomic P action was not ruled out since P bound to a cytosolic protein which showed characteristics of NGPR identified in other species in both mature and immature ovaries. In summary, gonadotrophins act on ovarian GC to induce the expression of genes which aid in the synthesis and activation of P and G. These steroids may act locally through genomic or non-genomic receptors mediating events which lead to follicle rupture. The presence of P, G and their receptors in the ovary after ovulation suggests a role for these anti-inflammatory steroids in the corpus luteum, perhaps remodelling the ruptured ovarian surface.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available