The insulin-like growth factor binding proteins (IGFBPs) are soluble proteins that bind insulin-like growth factors (IGFs)
with high affinity. Their principal functions are to regulate IGF availability in body fluids and tissues and to modulate IGF
binding to its receptors.By Northern blot analysis, Oh et al. (1996) found that mac25, or IGFBP7, is expressed as a 1.1-kb transcript in a broad
spectrum of normal tissues. These authors reported that the predicted 277-amino acid protein contains a 26-amino acid signal
sequence and the IGFBP motif (GCGCCXXC) at the N terminus. The IGFBP motif is located in a region containing a cluster
of 12 conserved cysteines, of which 11 are found in IGFBP7. The amino acid sequences of IGFBP7 and IGFBPs share 20 to
25% identity. Recombinant IGFBP7 specifically bound IGFs, although with relatively low affinity.
Kim et al. (1997) proposed that IGFBP7, CTGF , NOV , and IGFBP10 constitute a subfamily of
low-affinity IGFBPs.
NCBI Summary:
This gene encodes a member of the insulin-like growth factor (IGF)-binding protein (IGFBP) family. IGFBPs bind IGFs with high affinity, and regulate IGF availability in body fluids and tissues and modulate IGF binding to its receptors. This protein binds IGF-I and IGF-II with relatively low affinity, and belongs to a subfamily of low-affinity IGFBPs. It also stimulates prostacyclin production and cell adhesion. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, and one variant has been associated with retinal arterial macroaneurysm (PMID:21835307). [provided by RefSeq, Dec 2011]
General function
Ligand, Extracellular binding protein
Comment
Cellular localization
Secreted
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Ovarian function
Ovulation, Luteinization
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Inhibitory Effect of Insulin-like Growth Factor-binding Protein-7 (IGFBP7) on In Vitro Angiogenesis of Vascular Endothelial Cells in the Rat Corpus Luteum. Tamura K 2014 et al.
Angiogenesis in the developing corpus luteum (CL) is a prerequisite for establishment and maintenance of an early pregnancy. To explore the physiological significance of insulin-like growth factor-binding protein-7 (IGFBP7) in the developing CL, the effects of IGFBP7 on vascular endothelial growth factor (VEGFA)- and luteinizing hormone (LH)-induced in vitro tube formation were tested using isolated luteal microvascular endothelial cells (LECs). Capillary-like tube formation of LECs and their proliferation were stimulated by both VEGFA and LH. IGFBP7 treatment suppressed VEGFA- or LH-induced tube formation. The proliferation and migration of LECs, and phosphorylation of mitogen-activated protein kinase kinase and extracellular signal-regulated kinase 1/2 were inhibited by IGFBP7. Furthermore, IGFBP7 attenuated VEGFA-enhanced cyclooxygenase (COX)-2 mRNA expression and prostaglandin E2 secretion. These findings suggest the possibility that luteal IGFBP7 secretion may suppress the stimulatory effect of VEGFA on angiogenesis in the early CL.
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S.-A. Wandji, et al 2000 reported that messenger RNAs for MAC25 and Connective Tissue Growth Factor
(CTGF) Are Inversely Regulated during Folliculogenesis and Early Luteogenesis.
Granulosa cell mac25 mRNA expression was undetectable between the preantral and mid-antral stage but was strongly
induced in terminally differentiated granulosa cells of preovulatory follicles. Mac25 transcripts, which
were also abundant in ovarian blood vessels increased in the theca interna with follicular development. It was hypothesize that mac25, a tumor inhibitor, may promote terminal differentiation of granulosa cells
in preovulatory follicles.
Effect of Insulin-Like Growth Factor-Binding Protein 7 on Steroidogenesis in Granulosa Cells Derived from Equine Chorionic Gonadotropin-Primed Immature Rat Ovaries. Tamura K et al. Insulin-like growth factor (IGF) binding protein 7 (IGFBP7) is a secreted protein that regulates cellular proliferation, adhesion, and angiogenesis and has low affinity for IGF compared to IGFBP16. We sought to determine whether IGFBP7 is present in follicular fluid and to elucidate whether IGFBP7 participates in the steroidogenesis of rat mature follicles. Follicular fluid and granulosa cells (GCs) were collected from immature rats 2 days after their treatment with equine chorionic gonadotropin (eCG). IGFBP7 protein was detected in the follicular fluid and the conditioned medium of cultured ovarian granulosa cells by immunoblot analysis. When subconfluent GCs were cultured and treated with FSH and activin, co-incubation with FSH and activin markedly increased GC expression of Cyp19a1 (aromatase) mRNA and 17beta-estradiol secretion. The addition of recombinant murine IGFBP7 to these cultures decreased in the activin-enhanced FSH-stimulated Cyp19a1 mRNA levels in the cells and suppressed the 17beta-estradiol levels in the culture medium. Treatment of GCs with Igfbp7-specific siRNA, which knocked down Igfbp7 expression, increased the FSH-stimulated levels of Cyp19a1 but not Cyp11a1 expression. Basal and FSH-stimulated 17beta-estradiol secretion into the culture medium was also enhanced by Igfbp7 siRNA. These results suggest that IGFBP7 suppresses estrogen production in GCs. These observations support the notion that this protein, which is secreted into the follicular fluid, may serve as an intra-ovarian factor that negatively regulates GC differentiation.
Expression regulated by
LH
Comment
hCG-dependent regulation of angiogenic factors in human granulosa lutein cells. Phan B et al. As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and particularly in cancers. However, angiogenesis as a physiological process regularly occurs in the ovary. After ovulation the corpus luteum is formed by rapid vascularization of initially avascular granulosa lutein cell tissue. This process is regulated by gonadotropic hormones. In order to gain further insights in the regulatory mechanisms of angiogenesis in the ovary, we investigated these mechanisms in cell culture of human granulosa lutein cells. In particular, we determined the expression and production of several angiogenic factors including tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), Leptin, connective tissue growth factor (CTGF), meningioma-associated complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In addition, we showed that human chorionic gonadotropin (hCG) has distinct effects on their expression and production. hCG enhances the expression and production of TIMP-1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary. Mol. Reprod. Dev. (c) 2006 Wiley-Liss, Inc.
Ovarian localization
Granulosa, Theca, Luteal cells
Comment
Changes in mouse granulosa cell gene expression during early luteinization. McRae RS et al. Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.