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Bone Morphogenetic Proteins Are Mediators of Luteolysis in the Human Corpus Luteum

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Title: Bone Morphogenetic Proteins Are Mediators of Luteolysis in the Human Corpus Luteum
Authors: Nio-Kobayashi, Junko Browse this author →KAKEN DB
Trendell, Jennifer Browse this author
Giakoumelou, Sevasti Browse this author
Boswell, Lyndsey Browse this author
Nicol, Linda Browse this author
Kudo, Masataka Browse this author
Sakuragi, Noriaki Browse this author →KAKEN DB
Iwanaga, Toshihiko Browse this author
Duncan, William Colin Browse this author
Issue Date: Apr-2015
Publisher: Endocrine Society
Journal Title: Endocrinology
Volume: 156
Issue: 4
Start Page: 1494
End Page: 1503
Publisher DOI: 10.1210/en.2014-1704
PMID: 25635621
Abstract: Bone morphogenetic proteins (BMPs), members of the transforming growth factor beta (TGF beta) superfamily, play important roles in folliculogenesis in various species; however, little is known about their role in luteal function. In this study, we investigated the expression, regulation, and effects of BMP2, BMP4, and BMP6 in carefully dated human corpora lutea and cultured human luteinized granulosa cells. The mRNA abundance of BMPs was increased in the regressing corpus luteum in vivo (P<.01-.001). Human chorionic gonadotropin (hCG) down-regulated BMP2, BMP4, and BMP6 transcripts both in vivo (P=.05-.001) and in vitro (P<.001), and decreased the mRNA abundance of BMP receptors (BMPR1A, BMPR1B, BMPR2; P<.05-.01) in vitro. Three BMPs were regulated by differential signaling pathways. H89, a protein kinase A inhibitor, increased the expression of both BMP2 (P<.05) and BMP4 (P<.05) while decreasing BMP6 (P<.01). PMA, a protein kinase C activator, decreased both BMP4 and BMP6 expression (P<.0001) while enhancing the mRNA abundance of BMP2 (P<.01). BMPs significantly down-regulated transcripts for LH/choriogonadotropin receptor (LHCGR; P<.001) and steroidogenic acute regulatory protein (STAR; P<.001), whereas up-regulating those of follicular stimulating hormone receptor (FSHR; P<.01) and aromatase (CYP19A1; P<.05-.01) in vitro, possessing an effect opposite to hCG but similar to Activin A. Like Activin A, BMP4 and BMP6 stimulated the expression of Inhibin/Activin subunits with a marked effect on INHBB expression (P<.05-.01). These data confirm that BMPs are increased during luteal regression and negatively regulated by hCG via differential mechanisms, suggesting that BMPs are one of the mediators of luteolysis in women.
Description: Supplemental data is online at
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Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 小林 純子

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