Anti-Mullerian hormone (AMH) is induced by bone morphogenetic protein (BMP) cytokines in human granulosa cells.
OBJECTIVE
Serum concentration of anti-Mullerian hormone (AMH) is used as a biomarker in clinical practice. Therefore, it is important to elucidate the mechanism by which AMH is regulated in granulosa cells (GC). An important first step in understanding AMH regulation is to determine which factors up-regulate AMH expression.


METHODS
Human GC, obtained from 28 women undergoing oocyte retrieval for in vitro fertilization, were stimulated with various intraovarian cytokines including bone morphogenetic protein (BMP)-2, -6, -7 -15, activin-A and growth differentiation factor (GDF)-9 (100 ng/ml). The expression of AMH mRNA was evaluated with reverse transcription and quantitative real-time polymerase chain reaction (PCR), and AMH protein in cultured supernatant was measured with EIA kit.


RESULTS
BMP-2, -6, -7 and -15, but not activin-A and GDF-9, significantly induced AMH expression in GC at mRNA and protein level, while all stimuli increased FSH receptor mRNA and decreased steroidogenic acute regulatory protein (StAR) mRNA level.


CONCLUSIONS
Among the transforming growth factor (TGF)-β superfamily, BMP-2, -6, -7 and -15 significantly induced AMH expression in human GC.
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
Sayaka
S
Ogura-Nose
Osamu
O
Yoshino
Yutaka
Y
Osuga
Jia
J
Shi
Hisahiko
H
Hiroi
Tetsu
T
Yano
Yuji
Y
Taketani
D054304:Anti-Mullerian Hormone / Q000096:biosynthesis*; D055430:Bone Morphogenetic Protein 15 / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D055418:Bone Morphogenetic Protein 6 / Q000494:pharmacology; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D010750:Phosphoproteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011962:Receptors, FSH / Q000096:biosynthesis; D015854:Up-Regulation; D000098682:Steroidogenic Acute Regulatory Protein
C525718:BMP2 protein, human; C525816:BMP6 protein, human; D055430:Bone Morphogenetic Protein 15; D055396:Bone Morphogenetic Protein 2; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011962:Receptors, FSH; D000098682:Steroidogenic Acute Regulatory Protein; D054304:Anti-Mullerian Hormone