Biomaterial Database

Growth differentiation factor-9 induces Smad2 activation and inhibin B production in cultured human granulosa-luteal cells. 2003

Noora Kaivo-Oja, and Jonas Bondestam, and Meerit Kämäräinen, and Janne Koskimies, and Ursula Vitt, and Mark Cranfield, and Kaisa Vuojolainen, and Janne P Kallio, and Vesa M Olkkonen, and Masaru Hayashi, and Aristidis Moustakas, and Nigel P Groome, and Peter ten Dijke, and Aaron J W Hsueh, and Olli Ritvos

Program for Developmental and Reproductive Biology, Biomedicum Helsinki, and Department of Bacteriology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland.

The TGF beta family member growth differentiation factor-9 (GDF-9) is an oocyte-derived factor that is essential for mammalian ovarian folliculogenesis. GDF-9 mRNAs have been shown to be expressed in the human ovarian follicle from the primary follicle stage onward, and recombinant GDF-9 has been shown to promote human ovarian follicle growth in vitro. In this study with primary cultures of human granulosa-luteal (hGL) cells, we investigated whether recombinant GDF-9 activates components of the Smad signaling pathways known to be differentially activated by TGF beta and the bone morphogenetic proteins (BMPs). As with TGF beta, GDF-9 treatment caused the phosphorylation of endogenous 53-kDa proteins detected in Western blots with antiphospho-Smad2 antibodies (alpha PS2). However, unlike BMP-2, GDF-9 did not activate the phosphorylation of antiphospho-Smad1 antibody (alphaPS1)-immunoreactive proteins in hGL cells. Infection of hGL cells with an adenovirus expressing Smad2 (Ad-Smad2) confirmed that GDF-9 activates specifically phosphorylation of the Smad2 protein. Infection of hGL cells with Ad-Smad7, which expresses the inhibitory Smad7 protein, suppressed the levels of both GDF-9-induced endogenous and adenoviral alpha PS2-reactive proteins. Furthermore, GDF-9 increased the steady state levels of inhibin beta(B)-subunit mRNAs in hGL cells and strongly stimulated the secretion of dimeric inhibin B. Again, Ad-Smad7 blocked GDF-9-stimulated inhibin B production in a concentration-dependent manner. We identify here for the first time distinct molecular components of the GDF-9 signaling pathway in the human ovary. Our data suggest that GDF-9 mediates its effect through the pathway commonly activated by TGF beta and activin, but not that activated by many BMPs. The results are also consistent with the suggestion that in addition to endocrine control of inhibin production by gonadotropins, a local paracrine control of inhibin production is likely to occur via oocyte-derived factors in the human ovary.

UI	MeSH Term	Description	Entries
D007265	Inhibins	Glycoproteins that inhibit pituitary FOLLICLE STIMULATING HORMONE secretion. Inhibins are secreted by the Sertoli cells of the testes, the granulosa cells of the ovarian follicles, the placenta, and other tissues. Inhibins and ACTIVINS are modulators of FOLLICLE STIMULATING HORMONE secretions; both groups belong to the TGF-beta superfamily, as the TRANSFORMING GROWTH FACTOR BETA. Inhibins consist of a disulfide-linked heterodimer with a unique alpha linked to either a beta A or a beta B subunit to form inhibin A or inhibin B, respectively	Female Inhibin,Inhibin,Inhibin-F,Inhibins, Female,Inhibins, Testicular,Ovarian Inhibin,Testicular Inhibin,Female Inhibins,Inhibin F,Inhibin, Female,Inhibin, Ovarian,Inhibin, Testicular,Testicular Inhibins
D008184	Luteal Cells	PROGESTERONE-producing cells in the CORPUS LUTEUM. The large luteal cells derive from the GRANULOSA CELLS. The small luteal cells derive from the THECA CELLS.	Lutein Cells,Granulosa-Luteal Cells,Granulosa-Lutein Cells,Large Luteal Cells,Small Luteal Cells,Theca-Luteal cells,Theca-Lutein Cells,Cell, Granulosa-Luteal,Cell, Granulosa-Lutein,Cell, Large Luteal,Cell, Luteal,Cell, Lutein,Cell, Small Luteal,Cell, Theca-Lutein,Cells, Granulosa-Luteal,Cells, Granulosa-Lutein,Cells, Large Luteal,Cells, Luteal,Cells, Lutein,Cells, Small Luteal,Cells, Theca-Lutein,Granulosa Luteal Cells,Granulosa Lutein Cells,Granulosa-Luteal Cell,Granulosa-Lutein Cell,Large Luteal Cell,Luteal Cell,Luteal Cell, Large,Luteal Cell, Small,Luteal Cells, Large,Luteal Cells, Small,Lutein Cell,Small Luteal Cell,Theca Luteal cells,Theca Lutein Cells,Theca-Luteal cell,Theca-Lutein Cell,cell, Theca-Luteal,cells, Theca-Luteal
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000256	Adenoviridae	A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.	Adenoviruses,Ichtadenovirus,Adenovirus,Ichtadenoviruses
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia