NCBI Summary:
The protein encoded by this gene is a member of the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. This group of proteins is characterized by a polybasic proteolytic processing site which is cleaved to produce a mature protein containing seven conserved cysteine residues. The members of this family are regulators of cell growth and differentiation in both embryonic and adult tissues. The function of this protein is unknown, but expression studies suggest it may be involved in regulation of the adult lymphatic and erythroid systems and embryonic development.
General function
Ligand, Cytokine
Comment
Cellular localization
Secreted
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Ovarian function
Germ cell development
Comment
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. Shi J et al. OBJECTIVE: To examine the relevance of growth differentiation factor 3 (GDF-3) and bone morphogenetic protein (BMP) cytokines in human ovary. DESIGN: Molecular studies. SETTING: Research laboratory. PATIENT(S): Eight women undergoing salpingo-oophorectomy and 30 women undergoing ovarian stimulation for invitro fertilization. INTERVENTION(S): 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. RESULT(S): In the ovary, BMP cytokines, of the transforming growth factor beta (TGF-) superfamily, are known as a luteinization inhibitor by suppressing LH receptor expression in GC. Growth differentiation factor 3, a TGF- 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 invitro 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. CONCLUSION(S): GDF-3, induced with BMP-6 and BMP-7, might play a role in folliculogenesis by inhibiting the effect of BMP cytokines.
Expression regulated by
Growth Factors/ cytokines, BMP6,7
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Ovarian localization
Primordial Germ Cell
Comment
Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma
Clark AT, et al .
Genes required to maintain pluripotency in human embryonic stem (hES) cells are largely unknown, with the exception of OCT-4, a homolog of mouse Oct-4, which is critical for the establishment of the embryonic inner cell mass and the generation of totipotent mouse embryonic stem (mES) cell lines. In the current study, we identified two genes with expression similar to OCT-4, in that they are largely restricted to pluripotent hES cells, premeiotic germ lineage cells, and testicular germ cell tumor cells. Furthermore, we determined that upon hES cell differentiation, their expression is downregulated. The genes we identified in the current study include the human stella-related (STELLAR) gene, which encodes a highly divergent protein (with just 32.1% identity to mouse stella over the 159 amino acid sequence) that maps to human chromosome 12p13. Notably, human STELLAR is located distal to a previously uncharacterized homeobox gene, which is the human homolog of the recently identified murine gene, Nanog, and proximal to the GDF3 locus, whose transcription is restricted to germ cell tumor cells. Our characterization of STELLAR, NANOG, and GDF3 suggests that they may play a similar role in humans as in mice, in spite of their remarkable evolutionary divergence.
GDF3 was found in both embryonic and adult ovaries.