内分泌学
内科学
抗苗勒氏激素
生物
生长分化因子-9
骨形态发生蛋白15
卵巢
窦卵泡
骨形态发生蛋白
激素
卵泡发生
医学
细胞生物学
基因
骨形态发生蛋白7
胚胎
胚胎发生
生物化学
作者
Pierre Aimar,Anthony Estienne,Chrystèle Racine,Jean‐Yves Picard,Rénato Fanchin,Belén Lahoz Crespo,J. L. Alabart,J. Folch,Peggy Jarrier,Stéphane Fabre,Danielle Monniaux,Nathalie di Clemente
摘要
Anti-Müllerian hormone (AMH) is produced by the granulosa cells (GCs) of growing follicles and inhibits follicular development.This study aimed to investigate the regulation of the AMH-specific type 2 receptor (AMHR2) gene expression in GCs by bone morphogenetic protein (BMP)15, BMP4 and growth differentiation factor (GDF)9.Their effects on AMHR2 and AMH mRNAs were studied in luteinized human GCs and in ovine GCs (oGCs) from small antral follicles. The effects of BMPs on human AMHR2 and AMH promoter reporter activities were analyzed in transfected oGCs. The in vivo effect of BMP15 on GCs AMHR2 and AMH expression was investigated by using Lacaune and Rasa Aragonesa hyperprolific ewes carrying loss-of-function mutations in BMP15.mRNAs were quantified by real-time RT-PCR. Promoter reporter constructs activities were quantified by the measurement of their luciferase activity.BMP15 and BMP4 enhanced AMHR2 and AMH expression in human GCs and in oGCs, whereas GDF9 had no effect. In oGCs, GDF9 increased BMP15 effect on AMH expression. Consistent with these results, BMP15 and BMP4, but not GDF9, enhanced AMHR2 promoter activity in oGCs, whereas GDF9 increased BMP15 effect on AMH promoter activity. Moreover, oGCs from both BMP15 mutant ewes had reduced AMHR2 mRNA levels but unchanged AMH expression compared with wild-type ewes.Altogether, these results suggest that the mechanisms of action of BMP15 on AMHR2 and AMH expression are different, and that by stimulating AMHR2 and AMH expression in GCs BMP15 enhances AMH inhibitory actions in GCs.
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