Progesterone-Receptor Antagonists and Statins Decrease De Novo Cholesterol Synthesis and Increase Apoptosis in Rat and Human Periovulatory Granulosa Cells In Vitro1
| Autor: | D. G. Joakim Larsson, Eva Ch. Nielsen, Per-Arne Svensson, Björn Carlsson, Ruijin Shao, Emilia Rung, P. Anders Friberg, Håkan Billig, Lena M. S. Carlsson |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Cholesterol Granulosa cell Cell Biology General Medicine Biology chemistry.chemical_compound Mevastatin medicine.anatomical_structure Endocrinology Reproductive Medicine chemistry Simvastatin Apoptosis Internal medicine Progesterone receptor medicine lipids (amino acids peptides and proteins) Lovastatin Ovarian follicle medicine.drug |
| Zdroj: | Biology of Reproduction. 72:538-545 |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1095/biolreprod.104.033878 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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