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BOR - Papers in Press, published online ahead of print January 23, 2008.
Biol Reprod 2008, 10.1095/biolreprod.107.065656
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Submitted September 19, 2007
Returned for revision October 20, 2007
Accepted January 11, 2008

Ovary


Cortisol Is a Suppressor of Apoptosis in Bovine Corpus Luteum

Junichi Komiyama , Ryo Nishimura , Hwa-Yong Lee , Ryosuke Sakumoto , Masafumi Tetsuka , Tomas J. Acosta , Dariusz J. Skarzynski , and Kiyoshi Okuda *

* To whom correspondence should be addressed. E-mail: kokuda{at}cc.okayama-u.ac.jp.

Abstract
Glucocorticoid (GC) acts as a modulator of physiological functions in several organs. In the present study, we examined whether GC suppresses luteolysis in bovine corpus luteum (CL). Cortisol (an active GC) reduced the mRNA expression of caspase 8 (CASP8) and caspase 3 (CASP3), and reduced the enzymatic activity of CASP3 and cell death induced by tumor necrosis factor (TNF) and interferon gamma (IFNG) in cultured bovine luteal cells. mRNAs and proteins of GC receptor (NR3C1), 11beta-hydroxysteroid dehydrogenase type1 (HSD11B1) and HSD11B2 were expressed in CL throughout the estrous cycle. Moreover, the protein expression and the enzymatic activity of HSD11B1 were high at the early and the mid luteal stages compared to the regressed luteal stage. These results suggest that cortisol suppresses TNF-IFNG-induced apoptosis in vitro by reducing apoptosis signals via CASP8 and CASP3 in bovine CL, and that the local increase in cortisol production resulting from increased HSD11B1 at the early and mid luteal stages helps to maintain CL function by suppressing apoptosis of luteal cells.

Key words: Apoptosis • Corpus luteum • Glucocorticoid receptor • Cattle • Glucocorticoid





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