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Progesterone-recept...
Progesterone-receptor antagonists and statins decrease de novo cholesterol synthesis and increase apoptosis in rat and human periovulatory granulosa cells in vitro
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- Rung, Emilia, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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- Friberg, P. Anders, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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- Shao, Linus Ruijin, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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- Larsson, D. G. Joakim, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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- Nielsen, Eva Ch. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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- Svensson, Per-Arne, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för kroppssammansättning och metabolism,Institute of Internal Medicine, Dept of Body Composition and Metabolism
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- Carlsson, Björn, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för kroppssammansättning och metabolism,Institute of Internal Medicine, Dept of Body Composition and Metabolism
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- Carlsson, Lena M S, 1957 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för kroppssammansättning och metabolism,Institute of Internal Medicine, Dept of Body Composition and Metabolism
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- Billig, Håkan, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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(creator_code:org_t)
- Oxford University Press (OUP), 2005
- 2005
- English.
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In: Biology of reproduction. - : Oxford University Press (OUP). - 0006-3363 .- 1529-7268. ; 72:3, s. 538-45
- Related links:
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https://academic.oup...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Progesterone-receptor (PR) stimulation promotes survival in rat and human periovulatory granulosa cells. To investigate the mechanisms involved, periovulatory rat granulosa cells were incubated in vitro with or without the PR-antagonist Org 31710. Org 31710 caused the expected increase in apoptosis, and expression profiling using cDNA microarray analysis revealed regulation of several groups of genes with functional and/or metabolic connections. This regulation included decreased expression of genes involved in follicular rupture, increased stress responses, decreased angiogenesis, and decreased cholesterol synthesis. A decreased cholesterol synthesis was verified in experiments with both rat and human periovulatory granulosa cells treated with the PR-antagonists Org 31710 or RU 486 by measuring incorporation of [14C]acetate into cholesterol, cholesterol ester, and progesterone. Correspondingly, specific inhibition of cholesterol synthesis in periovulatory rat granulosa cells using 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (lovastatin, mevastatin, or simvastatin) increased apoptosis, measured as DNA fragmentation and caspase-3/7 activity. The increase in apoptosis caused by simvastatin was reversed by addition of the cholesterol synthesis-intermediary mevalonic acid. These results show that PR antagonists reduce cholesterol synthesis in periovulatory granulosa cells and that cholesterol synthesis is important for granulosa cell survival.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- Animals
- Apoptosis/drug effects/*physiology
- Cell Survival/physiology
- Cholesterol/*biosynthesis
- Estrenes/pharmacology
- Female
- Furans/pharmacology
- Gene Expression Profiling
- Gene Expression Regulation
- Granulosa Cells/drug effects/*metabolism
- Hormone Antagonists/pharmacology
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
- Mifepristone/pharmacology
- Oligonucleotide Array Sequence Analysis
- Ovulation/*physiology
- Rats
- Rats
- Sprague-Dawley
- Receptors
- Progesterone/antagonists & inhibitors/*metabolism
- Signal Transduction/physiology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Rung, Emilia, 19 ...
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Friberg, P. Ande ...
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Shao, Linus Ruij ...
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Larsson, D. G. J ...
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Nielsen, Eva Ch.
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Svensson, Per-Ar ...
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Carlsson, Björn, ...
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Carlsson, Lena M ...
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Billig, Håkan, 1 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
- Articles in the publication
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Biology of repro ...
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University of Gothenburg