The role of metalloproteinases in TIMP's in the physiological control of human corpus luteum
The role of metalloproteinases in TIMP's in the physiological control of human corpus luteum
The cellular mechanisms involved in luteal regression and human chorionic gonadotrophin (hCG) induced rescue of the corpus luteum are largely unknown. Recently, several publications have pointed to a central role for the extra-cellular matrix (ECM) in corpus luteum function. A greater understanding of the basic biochemistry of matrix degradation has shown that this is controlled by the release of matrix metalloproteinases (MMP's) which are, in turn, controlled by tissue inhibitors of metalloproteinases (TIMP's). I hypothesise that the mechanisms of corpus luteum regression are mediated through interactions between the luteal cells and the ECM.
The hypothesis is tested using an established granulosa cell culture system which provides an in vitro model for corpus luteum function and also using samples of corpus luteum. In testing this hypothesis the phenomenon of granulosa cell detachment from an ECM in the presence or absence of gonadotrophin is studied. Furthermore I identify which MMP's and TIMP's are produced by granulosa cells and establish that gonadotrophin can influence their activity. The methodology utilises the granulosa cell culture media with subsequent analysis by zymography western blot analysis and immunocytochemistry. Qualitative analysis is achieved using light, electron and confocal microscopy while quantitative analysis uses ELISA.
The data presented shows increased granulosa cell retention onto the ECM and progesterone production in the presence of hCG. Cell retention is greater when ECM is plated onto plastic rather than glass. Analysis of the media demonstrates the presence of predominantly MMP-9 and also MMP-2. TIMP-1 is also identified.
It would appear that luteolysis is mediated via ECM degradation resulting from a shift in the balance of MMP and TIMP activity. I suggest that luteal rescue by hCG occurs as a result of a maintenance in ECM stability mediated by reduced MMP and elevated TIMP levels.
University of Southampton
O'Sullivan, Mark Jonathan Benjamin
1997
O'Sullivan, Mark Jonathan Benjamin
O'Sullivan, Mark Jonathan Benjamin
(1997)
The role of metalloproteinases in TIMP's in the physiological control of human corpus luteum.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The cellular mechanisms involved in luteal regression and human chorionic gonadotrophin (hCG) induced rescue of the corpus luteum are largely unknown. Recently, several publications have pointed to a central role for the extra-cellular matrix (ECM) in corpus luteum function. A greater understanding of the basic biochemistry of matrix degradation has shown that this is controlled by the release of matrix metalloproteinases (MMP's) which are, in turn, controlled by tissue inhibitors of metalloproteinases (TIMP's). I hypothesise that the mechanisms of corpus luteum regression are mediated through interactions between the luteal cells and the ECM.
The hypothesis is tested using an established granulosa cell culture system which provides an in vitro model for corpus luteum function and also using samples of corpus luteum. In testing this hypothesis the phenomenon of granulosa cell detachment from an ECM in the presence or absence of gonadotrophin is studied. Furthermore I identify which MMP's and TIMP's are produced by granulosa cells and establish that gonadotrophin can influence their activity. The methodology utilises the granulosa cell culture media with subsequent analysis by zymography western blot analysis and immunocytochemistry. Qualitative analysis is achieved using light, electron and confocal microscopy while quantitative analysis uses ELISA.
The data presented shows increased granulosa cell retention onto the ECM and progesterone production in the presence of hCG. Cell retention is greater when ECM is plated onto plastic rather than glass. Analysis of the media demonstrates the presence of predominantly MMP-9 and also MMP-2. TIMP-1 is also identified.
It would appear that luteolysis is mediated via ECM degradation resulting from a shift in the balance of MMP and TIMP activity. I suggest that luteal rescue by hCG occurs as a result of a maintenance in ECM stability mediated by reduced MMP and elevated TIMP levels.
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Published date: 1997
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Local EPrints ID: 463064
URI: http://eprints.soton.ac.uk/id/eprint/463064
PURE UUID: ff8168e9-f09d-4647-ae0b-6fa15b90167c
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Date deposited: 04 Jul 2022 20:43
Last modified: 04 Jul 2022 20:43
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Author:
Mark Jonathan Benjamin O'Sullivan
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