The Effect of Luteal “Rescue” on the Expression and Localization of Matrix Metalloproteinases and Their Tissue Inhibitors in the Human Corpus Luteum

Duncan, W. Colin; McNeilly, Alan S.; Illingworth, Peter

doi:10.1210/jcem.83.7.4950

Cited by 28 publications

(21 citation statements)

References 54 publications

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“…For example, MMP-9 activity peaks in both early and late luteal phases and MMP-2 activity is maximal in the late corpus luteum, when vessels are regressing (Duncan et al, 1998). A similar observation was made in the endometrium, in which MMPs are overexpressed during the late menstrual phase, when hemorrhage occurs as a result of vessel breakdown (Salamonsen, 1994).…”

Section: Matrix Metalloproteinases and Vascularsupporting

confidence: 56%

“…Recent studies have shown that MMPs are overexpressed not only during angiogenesis, but also during the involution and/or breakdown of vascularized organs such as the corpus luteum, the endometrium, and the mammary gland (Ambili et al, 1998;Duncan et al, 1998;Salamonsen, 1994). These findings suggest that proteolytic enzymes may play an important role not only in the initial phases of angiogenesis, but also in the later stages of this process when microvessels no longer proliferate and are gradually reabsorbed.…”

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confidence: 99%

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Regulation of Vascular Growth and Regression by Matrix Metalloproteinases in the Rat Aorta Model of Angiogenesis

Zhu

Guo

Villaschi

et al. 2000

Laboratory Investigation

117

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SUMMARY:Matrix metalloproteinases (MMPs) have been implicated in the formation of microvessels during angiogenesis, but their role in vascular regression is poorly understood. The rat aorta model of angiogenesis was used to study the function of MMPs at different stages of the angiogenic process. Gelatin zymography and Western analysis demonstrated production of MMP-2 and MMP-9 by aortic outgrowths in serum-free collagen gel culture. MMP-2 was found in both culture medium and collagen gel, whereas MMP-9 was predominantly associated with the gel. MMP expression increased gradually during the angiogenic growth phase and stayed high when vessels regressed and collagen lysed around the aortic rings. The MMP inhibitors, batimastat and marimastat, blocked formation of microvessels when added to the culture medium at the beginning of the experiment. They, however, stabilized the microvessels and prevented vascular regression after the angiogenic growth phase. This effect was observed also under conditions of angiogenic stimulation by basic fibroblast growth factor. MMP inhibitormediated stabilization of microvessels was associated with inhibition of collagen lysis and accumulation of collagen fibrils in the subendothelial space. This study demonstrates that MMPs promote microvessel formation during the early stages of angiogenesis, but also contribute to the reabsorption of the neovasculature in the later stages of this process. The time-dependent divergent effects of MMPs on microvessel growth and survival may influence the in vivo activity of MMP inhibitors used to treat angiogenesis-dependent disorders. (Lab Invest 2000, 80:545-555).

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Section: Matrix Metalloproteinases and Vascularsupporting

confidence: 56%

mentioning

confidence: 99%

Regulation of Vascular Growth and Regression by Matrix Metalloproteinases in the Rat Aorta Model of Angiogenesis

Zhu

Guo

Villaschi

et al. 2000

Laboratory Investigation

117

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“…In addition, archival corpora lutea that had been immediately frozen and stored at K70 8C from previous studies (Duncan et al 2005b were also available. Frozen tissue quarters for mRNA extraction were available from three early luteal, seven mid-luteal, six late luteal and five corpora lutea that had been 'rescued' (women were given daily doubling doses of exogenous hCG (Serono Laboratories, Welwyn Garden City, UK), starting at 125 IU, from LHC7 for 5-8 days until surgery) as described previously (Duncan et al 1996(Duncan et al , 1998b.…”

Section: Collection Of Human Ovarian Tissue and Human Corpora Luteamentioning

confidence: 99%

“…In simulated early pregnancy, human chorionic gonadotrophin (hCG) has effects on immune cells, endothelial cells and fibroblasts (Duncan et al 1998a, 1998b, Duncan 2000, Wulff et al 2001) which do not express LH/hCG receptors (LHCGR). Therefore, if paracrine molecules, which are regulated by hCG, are involved in luteolysis, these molecules should be the products of steroidogenic cells and have receptors on target cells.…”

Section: Introductionmentioning

confidence: 99%

Expression and regulation of oestrogen receptors in the human corpus luteum

Driesche¹,

Smith²,

Myers³

et al. 2008

Reproduction

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The molecular mechanisms underlying the control of corpus luteum lifespan in women are not fully understood. Oestradiol has various luteolytic, or luteotrophic, functions in some species, and as it is synthesised within the human corpus luteum, it is an excellent candidate molecule to be a paracrine regulator of luteal function. This study aimed to comprehensively investigate the expression, regulation and effects of oestrogen receptors (ER) in human luteal cells. Genomic oestrogen receptors ERa, ERb1 and ERb2 were immunolocalised in human corpora lutea from throughout the luteal phase. mRNA expression was investigated throughout the luteal phase and after luteal rescue with exogenous human chorionic gonadotrophin (hCG). The regulation of ER expression and oestradiol action was investigated in cultures of luteinised granulosa cells. ER subtypes ERb1 and ERb2 were localised throughout the luteal phase to steroidogenic cells in the human corpus luteum and cells of the surrounding stroma. Unlike follicular granulosa cells, steroidogenic cells in the corpus luteum showed minimal ERa immunostaining. The presence of endothelial cells in the granulosa cell layer with ERb1 and ERb2 positive nuclei was noted. ERb1 and ERb2 were differentially regulated across the luteal phase with ERb1 maximally expressed in the mid-luteal phase, while ERb2 expression was maximal in the early luteal phase. In vivo and in vitro, hCG had no long-term effect on ER expression, although in vitro hCG and oestradiol acutely down-regulated ERs. Treatment with oestradiol in vitro down-regulated 11b-hydroxysteroid dehydrogenase type 1 and inhibin bA subunit confirming a functional oestradiol response. These data highlight functional and differentially regulated oestradiol reception in human luteal cells.

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“…The molecular events involved in luteolysis and how they are prevented by exposure to human chorionic gonadotrophin (hCG) remain unclear (Behrman et al 1993, Duncan 2000. As hCG has effects on macrophages (Duncan et al 1998a), fibroblasts (Duncan et al 1998b) and blood vessels (Wulff et al 2001), that do not express luteinising hormone (LH)/hCG receptors, paracrine molecules must have important roles in luteal function (Duncan 2000).…”

Section: Introductionmentioning

confidence: 99%

The effect of human chorionic gonadotrophin on the expression of progesterone receptors in human luteal cells in vivo and in vitro

Duncan¹,

Gay²,

Maybin³

2005

Reproduction

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The human corpus luteum expresses genomic progesterone receptors (PRs) suggesting that progesterone may have an autocrine or paracrine role in luteal function. We hypothesised that the reduction in luteal PR reported in the late-luteal phase augmented progesterone withdrawal and had a role in luteolysis. We therefore tested the hypothesis that luteal rescue with human chorionic gonadotrophin (hCG) would maintain PR expression. PR was immunolocalised to different cell types in human corpora lutea (n 5 35) from different stages of the luteal phase and after luteal rescue with exogenous hCG. There was no change in the staining intensity of theca-lutein cell or stromal cell PR throughout the luteal phase or after luteal rescue. In the late-luteal phase, granulosa-lutein cell PR immunostaining was reduced (P < 0.05) but the trend to reduction was also seen after luteal rescue with hCG (P 5 0.055). To further investigate the effect of hCG on granulosa-lutein cell PR expression, an in vitro model system of cultured human luteinised granulosa cells was studied. Cells were cultured for 12 -13 days exposed to different patterns of hCG and aminoglutethamide to manipulate progesterone secretion (P < 0.0001). Expression of PR A/B and PR B isoforms was examined by quantitative real-time RT-PCR. PR A/B mRNA was lower (P < 0.05) after 11 -13 days of culture than after 7 days of culture. This reduction could not be prevented by hCG in the presence (P < 0.05) or absence (P < 0.05) of stimulated progesterone secretion. The expression of PR B mRNA showed a similar pattern (P 5 0.054). Simulated early pregnancy in vivo and hCG treatment of luteinised granulosa cells in vitro did not appear to prevent the down-regulation of PR seen during luteolysis.

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The Effect of Luteal “Rescue” on the Expression and Localization of Matrix Metalloproteinases and Their Tissue Inhibitors in the Human Corpus Luteum

Cited by 28 publications

References 54 publications

Regulation of Vascular Growth and Regression by Matrix Metalloproteinases in the Rat Aorta Model of Angiogenesis

Regulation of Vascular Growth and Regression by Matrix Metalloproteinases in the Rat Aorta Model of Angiogenesis

Expression and regulation of oestrogen receptors in the human corpus luteum

The effect of human chorionic gonadotrophin on the expression of progesterone receptors in human luteal cells in vivo and in vitro

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