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Cyclooxygenase‐2 is acutely induced by CCAAT/enhancer‐binding protein β to produce prostaglandin E 2 and F 2α following gonadotropin stimulation in Leydig cells
Author(s) -
Yazawa Takashi,
Imamichi Yoshitaka,
Yuhki Kohichi,
Uwada Junsuke,
Mikami Daisuke,
Shimada Masayuki,
Miyamoto Kaoru,
Kitano Takeshi,
Takahashi Satoru,
Sekiguchi Toshio,
Suzuki Nobuo,
Rafiqul Islam Khan Md.,
Ushikubi Fumitaka,
Umezawa Akihiro,
Taniguchi Takanobu
Publication year - 2019
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.23163
Subject(s) - biology , human chorionic gonadotropin , endocrinology , medicine , prostaglandin , leydig cell , ccaat enhancer binding proteins , cyclooxygenase , prostaglandin e2 , microbiology and biotechnology , transcription factor , hormone , luteinizing hormone , enzyme , gene , nuclear protein , biochemistry
Abstract Cyclooxygenase 2 (COX‐2) is an inducible rate‐limiting enzyme for prostanoid production. Because COX‐2 represents one of the inducible genes in mouse mesenchymal stem cells upon differentiation into Leydig cells, we investigated COX‐2 expression and production of prostaglandin (PG) in Leydig cells. Although COX‐2 was undetectable in mouse testis, it was transiently induced in Leydig cells by human chorionic gonadotropin (hCG) administration. Consistent with the finding that Leydig cells expressed aldo‐keto reductase 1B7 (PGF synthase) and PGE synthase 2, induction of COX‐2 by hCG caused a marked increase in testicular PGF 2α and PGE 2 levels. Using mouse Leydig cell tumor‐derived MA‐10 cells as a model, it was indicated by reporter assays and electron mobility shift assays that transcription of the COX‐2 gene was activated by CCAAT/enhancer‐binding protein β (C/EBPβ) with cAMP‐stimulation. C/EBPβ expression was induced by cAMP‐stimulation, whereas expression of C/EBP homolog protein (CHOP) was robustly downregulated. Transfection of CHOP expression plasmid inhibited cAMP‐induced COX‐2 promoter activity. In addition, CHOP reduced constitutive COX‐2 expression in other mouse Leydig cell tumor‐derived TM3 cells. These results indicate that COX‐2 is induced in Leydig cells by activation of C/EBPβ via reduction of CHOP expression upon gonadotropin‐stimulation to produce PGF 2α and PGE 2 .

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