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.
Publication Date: 2000-07-25 PubMed ID: 10906042DOI: 10.1095/biolreprod63.2.390Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates how insulin-like growth factor (IGF) and certain peptides influence the breakdown of IGF-binding protein-4 (IGFBP-4) in the preovulatory follicles of cows, pigs, and horses.
Introduction to the Research
- This study follows up on previous work demonstrating that the breakdown of IGF-binding protein-4 (IGFBP-4) in sheep’s ovarian follicles is dependent on IGF and is controlled by a particular component (HBD) found in IGFBP-3 and in other growth factors and proteins.
- The current investigation expands this research to three other species – cows, pigs and horses – in an effort to understand the regulatory factors of this process in their ovarian follicles before ovulation.
Research Findings
- Findings from this study show that fluids from preovulatory follicles of all three species under study have the ability to break down IGFBP-4.
- The breakdown of IGFBP-4 was found to be enhanced when a surplus amount of IGF-I was present.
- The breakdown process was inhibited to varying degrees, by IGFBP-2 or -3 or monoclonal antibodies against IGF-I or -II.
- Interestingly, the inhibition was reversed in a dose-dependent manner when either IGF-I or -II was introduced.
Role of Heparin-Binding-Peptides and Domain Mutation
- Other regulatory factors were also explored in this study, including peptides containing a heparin-binding domain (HBD).
- Those derived from the C-terminal domain of IGFBP-3 or -5 were found to inhibit IGFBP-4 breakdown, as well as other peptides derived from various growth factors and proteins.
- One of the most significant findings is that even a slight mutation in the HBD of IGFBP-3 made it less successful at inhibiting IGFBP-4 degradation, which implies a precise mechanism at work.
Conclusion and Further Implications
- The overall findings suggest that as follicles develop to the preovulatory stage in cows, pigs, and horses, the increase in IGF availability might boost the breakdown of IGFBP-4.
- Differently, in atretic (shrinking or degenerating) follicles, the decrease in IGF availability, and the increased expression of others IGFBP might participate in decreasing IGFBP-4 degradation.
- This variation in IGFBP-4 degradation could play a role in follicle health, development, and animal reproduction.
- The findings prove potential for more work to uncover the role of other HBD-containing proteins in the regulation of enzymes that break down IGFBP-4.
Cite This Article
APA
Mazerbourg S, Zapf J, Bar RS, Brigstock DR, Monget P.
(2000).
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.
Biol Reprod, 63(2), 390-400.
https://doi.org/10.1095/biolreprod63.2.390 Publication
Researcher Affiliations
- Station INRA de Physiologie de la Reproduction des Mammifères Domestiques, URA CNRS 1291, 37380 Nouzilly, France.
MeSH Terms
- Animals
- Antibodies, Monoclonal / pharmacology
- Binding Sites
- Blood Coagulation Factors
- Carrier Proteins / pharmacology
- Cattle
- Connective Tissue Growth Factor
- Endopeptidases / metabolism
- Female
- Follicular Fluid / enzymology
- Growth Substances / pharmacology
- Heparin / metabolism
- Horses
- Immediate-Early Proteins / pharmacology
- Insulin-Like Growth Factor Binding Protein 2 / pharmacology
- Insulin-Like Growth Factor Binding Protein 3 / pharmacology
- Insulin-Like Growth Factor Binding Protein 4 / metabolism
- Insulin-Like Growth Factor Binding Protein 5 / pharmacology
- Insulin-Like Growth Factor I / pharmacology
- Insulin-Like Growth Factor II / pharmacology
- Intercellular Signaling Peptides and Proteins
- Ovarian Follicle / enzymology
- Ovulation
- Peptide Fragments / pharmacology
- RNA-Binding Proteins
- Ribosomal Proteins
- Somatomedins / pharmacology
- Swine
- Vitronectin / pharmacology
Citations
This article has been cited 3 times.- Yu X, Wang N, Wang X, Ren H, Zhang Y, Zhang Y, Qiu Y, Wang H, Wang G, Pei X, Chen P, Ren Y, Ha C, Wang L, Wang H. Oocyte Arrested at Metaphase II Stage were Derived from Human Pluripotent Stem Cells in vitro.. Stem Cell Rev Rep 2023 May;19(4):1067-1081.
- Mazerbourg S, Monget P. Insulin-Like Growth Factor Binding Proteins and IGFBP Proteases: A Dynamic System Regulating the Ovarian Folliculogenesis.. Front Endocrinol (Lausanne) 2018;9:134.
- Wex H, Ahrens D, Hohmann B, Redlich A, Mittler U, Vorwerk P. Insulin-like growth factor-binding protein 4 in children with acute lymphoblastic leukemia.. Int J Hematol 2005 Aug;82(2):137-42.
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