Progesterone-receptor antagonists and statins decrease de novo cholesterol synthesis and increase apoptosis in rat and human periovulatory granulosa cells in vitro

Biology of Reproduction
Emilia RungHåkan Billig

Abstract

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 ...Continue Reading

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Citations

Feb 12, 2014·Reproduction : the Official Journal of the Society for the Study of Fertility·John J Peluso, James K Pru
May 15, 2012·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Nicel TasdemirGulnur Ozaksit
Oct 24, 2013·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Yuval YungAriel Hourvitz
Feb 11, 2010·Molecular and Cellular Endocrinology·J J PelusoC A Wu
Oct 13, 2009·Molecular and Cellular Endocrinology·P Anders FribergHåkan Billig
Dec 3, 2014·The Journal of Reproduction and Development·Rei HirataKiyoshi Okuda
Sep 13, 2008·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Wuwen ZhangWen Wang
Nov 28, 2015·BMC Pregnancy and Childbirth·Abdulrahman Al-AjlanNasser M Al-Daghri
Jan 21, 2010·Nuclear Receptor Signaling·Rebecca L RobkerDarryl L Russell
Jul 27, 2006·Molecular Reproduction and Development·Emilia RungHåkan Billig
Sep 21, 2006·The Journal of Clinical Endocrinology and Metabolism·Lawrence EngmannJohn J Peluso
Feb 26, 2010·Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering·Marcela CapcarováShubhadeep Roychoudhury
Nov 9, 2012·Biology of Reproduction·Muraly PuttabyatappaCharles L Chaffin

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Methods Mentioned

BETA
Chip
chips
Assay

Software Mentioned

Affymetrix
Diff Call
blastn
Apo
Affymetrix GeneChip Analysis Suite
ONE
BLAST

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