title: Insulin-like growth factor (IGF)-binding protein-4 proteolytic degradation in bovine, equine, and porcine preovulatory follicles: regulation by IGFs and heparin-binding domain-containing peptides.
abstract: We recently showed that insulin-like growth factor-binding protein-4 (IGFBP-4) proteolytic degradation in ovine preovulatory ovarian follicles is IGF-dependent and regulated by the heparin-binding domain (HBD) from IGFBP-3 and from connective tissue growth factor (CTGF), heparan/heparin-interacting protein (HIP), and vitronectin. The present study investigated regulation of IGFBP-4 proteolytic degradation in porcine, bovine, and equine ovarian preovulatory follicles. Follicular fluid from such preovulatory follicles contains proteolytic activity, degrading exogenous IGFBP-4. An excess of IGF-I enhanced IGFBP-4 degradation. In contrast, IGFBP-2 or -3 or monoclonal antibodies against IGF-I or -II dose-dependently inhibited IGFBP-4 degradation, and IGF-I or -II reversed this inhibition in a dose-dependent manner. Heparin-binding peptides derived from the C-terminal domain of IGFBP-3 or -5 inhibited IGFBP-4 degradation. Other heparin-binding peptides derived from CTGF, HIP, and vitronectin also inhibited IGFBP-4 degradation, except in porcine follicles. Finally, IGFBP-3 that was mutated in its HBD was less effective at inhibiting IGFBP-4 degradation. Thus, in bovine, porcine, and equine preovulatory follicles, IGFBP-4 proteolytic degradation both depends on IGFs and is inhibited by peptides containing HBD. Overall, these results suggest that during terminal development of follicles to the preovulatory stage in domestic animal species, the increase in IGF bioavailability might enhance IGFBP-4 degradation. In contrast, in atretic follicles, the decrease in IGF bioavailability, resulting partly from the increase in IGFBP-2 (sow, heifer, mare) and IGFBP-5 (heifer) expression would participate in the decrease of IGFBP-4 degradation. In bovine atretic follicles, IGFBP-5 would also strengthen the inhibition of IGFBP-4 degradation by direct interaction of its HBD with the protease. The involvement of other HBD-containing proteins in the modulation of intrafollicular proteases degrading IGFBP-4 remains to be investigated.
authors.affiliation: Station INRA de Physiologie de la Reproduction des Mammifères Domestiques, URA CNRS 1291, 37380 Nouzilly, France.
authors.forename: S
authors.initials: S
authors.lastname: Mazerbourg
authors.forename: J
authors.initials: J
authors.lastname: Zapf
authors.forename: R S
authors.initials: RS
authors.lastname: Bar
authors.forename: D R
authors.initials: DR
authors.lastname: Brigstock
authors.forename: P
authors.initials: P
authors.lastname: Monget
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D001779:Blood Coagulation Factors; D002352:Carrier Proteins / Q000494:pharmacology; D002417:Cattle; D055513:Connective Tissue Growth Factor; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D015571:Follicular Fluid / Q000201:enzymology; D006133:Growth Substances / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism*; D006736:Horses; D017874:Immediate-Early Proteins / Q000494:pharmacology; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D006080:Ovarian Follicle / Q000201:enzymology*; D010060:Ovulation; D010446:Peptide Fragments / Q000494:pharmacology; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D013002:Somatomedins / Q000494:pharmacology*; D013552:Swine; D019096:Vitronectin / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D001779:Blood Coagulation Factors; D002352:Carrier Proteins; D006133:Growth Substances; D017874:Immediate-Early Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; C104946:RPL29 protein, human; D012269:Ribosomal Proteins; D013002:Somatomedins; D019096:Vitronectin; D055513:Connective Tissue Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D006493:Heparin; D010450:Endopeptidases