Growth differentiation factor 3 is induced by bone morphogenetic protein 6 (BMP-6) and BMP-7 and increases luteinizing hormone receptor messenger RNA expression in human granulosa cells

In the human ovary, GDF-3, an inhibitor of BMP cytokines, was detected in granulosa cells and oocytes, and its expression was regulated by BMP cytokines.


Jia Shi, M.D., Ph.D., Osamu Yoshino, M.D., Ph.D., Yutaka Osuga, M.D., Ph.D., Ikumi Akiyama, M.D., Miyuki Harada, M.D., Ph.D., Kaori Koga, M.D., Ph.D., Akihisa Fujimoto, M.D., Ph.D., Tetsu Yano, M.D., Ph.D., Yuji Taketani, M.D., Ph.D.

Volume 97, Issue 4, Pages 979-983



To examine the relevance of growth differentiation factor 3 (GDF-3) and bone morphogenetic protein (BMP) cytokines in human ovary.


Molecular studies.


Research laboratory.


Eight women undergoing salpingo-oophorectomy and 30 women undergoing ovarian stimulation for in vitro fertilization.


Localizing GDF-3 protein in human ovaries; granulosa cells (GC) cultured with GDF-3, BMP-6, or BMP-7 followed by RNA extraction.

Main Outcome Measure(s):

The localization of GDF-3 protein in normal human ovaries via immunohistochemical analysis, GDF-3 messenger RNA (mRNA) expression evaluation via quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR), and evaluation of the effect of GDF-3 on leuteinizing hormone (LH) receptor mRNA expression via quantitative real-time RT-PCR.


In the ovary, BMP cytokines, of the transforming growth factor beta (TGF-β) superfamily, are known as a luteinization inhibitor by suppressing LH receptor expression in GC. Growth differentiation factor 3, a TGF-β superfamily cytokine, is recognized as an inhibitor of BMP cytokines in other cells. Immunohistochemical analysis showed that GDF-3 was strongly detected in the GC of antral follicles. An in vitro assay revealed that BMP-6 or BMP-7 induced GDF-3 mRNA in GC. Also, GDF-3 increased LH receptor mRNA expression and inhibited the effect of BMP-7, which suppressed the LH receptor mRNA expression in GC.


GDF-3, induced with BMP-6 and BMP-7, might play a role in folliculogenesis by inhibiting the effect of BMP cytokines.

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