The DOI matches its Crossref record.
Evidence That the Insulin-Like Growth Factor Binding Protein-4 Protease in Human Ovarian Follicular Fluid Is Pregnancy Associated Plasma Protein-A
Abstract
Ovarian insulin-like growth factor binding protein-4 (IGFBP-4) proteolysis is involved in the regulation of follicular development, but until now the identity of the responsible enzyme was unknown. In this study, we identify the IGFBP4 protease in human follicular fluid as pregnancy associated plasma protein-A (PAPP-A) based on distinctive IGFBP-4 cleavage pattern, the same protease inhibitor profile, specific inhibition and immunodepletion of IGFBP-4 protease activity with PAPP-A polyclonal antibodies, and immunorecognition by PAPP-A monoclonal antibodies in ELISA. Furthermore, PAPP-A levels in estrogen-dominant and androgen-dominant follicular fluids reflect their IGFBP-4 proteolytic activity. PAPP-A was also secreted by human granulosa cells, the reputed source of IGFBP-4 protease activity in follicular fluid. We have the molecular and biochemical tools to begin to delineate the regulation and biological function of PAPP-A in normal and dysregulated follicular development and atresia.
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“A high concentration of this protein is found in the serum of pregnant women (Silahtaroglu et al. 1993; Conover et al. 1999; Lawrence et al. 1999).”
From Limb-Girdle Muscular Dystrophy Type 2H Associated with Mutation in TRIM32, a Putative E3-Ubiquitin–Ligase Gene (2002) · cites this paper as Conover et al. 1999
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Items 101–117 of 117
Mechanisms of Follicular Development: The Role of Gonadotrophins
Messinis, I. E. (2008) · Cambridge University Press eBooks · doi:10.1017/cbo9780511547287.005 · Cited by 5
Characterizing the Role of Endocannabinoid Receptor Cnr1 in Mouse Ovarian Granulosa Cells
Randhawa, J., Madogwe, E., McCall, A., et al. (2025) · Cell Biochemistry and Function · doi:10.1002/cbf.70070 · Cited by 4
Firouzabadi, R. D., Mohammadian, F., Mashayekhy, M., Davar, R., & Eftekhar, M. (2012) · Europe PMC (PubMed Central) · Cited by 3
Harland, A. J., & Perks, C. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104749 · Cited by 2
The effect of ligation of the ovarian artery on ovarian follicular function in rats.
Razi, M., Najafpour, A., Najafi, G., et al. (2009) · Iranian Journal of Veterinary Medicine · doi:10.22059/ijvm.2009.20632 · Cited by 2
Slomiany, M. G., & Rosenzweig, S. A. (2006) · Elsevier eBooks · doi:10.1016/b978-012088484-1/50007-0 · Cited by 1
The effect of follicular aging on gene expression in oocytes and granulosal cells.
Lingenfelter, B. M. (2008) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.9309
Does Endometriosis Affect PAPP-A Concentration in First Trimester Fetal Screening Test?
Corigliano, M. C., Martelli, F., Capogna, M. V., Bruno, A., Sorge, R. P., Sarta, S., Piccione, E., & Pietropolli, A. (2016) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.5301/je.5000249
“In particular, PAPP-A expression in ovary is limited to dominant follicles and the corpus luteum (28-34).”
BackgroundLimb girdle muscular dystrophy in the Hutterite population of North America
Frosk, P. (2005) · Mspace (University of Manitoba)
Hájek, P., & Maçek, M. (2010) · Cor et Vasa · doi:10.33678/cor.2010.120
Серебряная, Д. В., Adasheva, D. A., Konev, A. A., et al. (2021) · Biochemistry (Moscow) · doi:10.31857/s0320972521110026
Protein structure-aided prediction of the phylogenetic ancestry of genes. The case of IGF systemPreprint
Fouchécourt, S., Callebaut, I., & Monget, P. (2025) · Research Square · doi:10.21203/rs.3.rs-7721753/v1
Fouchécourt, S., Callebaut, I., & Monget, P. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5339359
Fouchécourt, S., Callebaut, I., & Monget, P. (2026) · Research Square · doi:10.21203/rs.3.rs-8732881/v1
The Critical Functions of FGF2, LIF and IGF1 in the Improvement of In Vitro Embryo Production
Mangiavacchi, P. M., Lee, K., & Redel, B. K. (2026) · Biomolecules · doi:10.3390/biom16040487
“Commonly secreted by granulosa cells, PAPP-A is directly associated with fertility parameters, such as the number of COCs produced and the levels of progesterone and estradiol during ovulation, and is thus considered a marker of follicular selection [138,139].”
GENE EXPRESSION PROFILING OF BOVINE OVARIAN FOLLICULAR SELECTION
Antoniou, E., Liu, Z., Youngquist, R. S., & Garverick, A. (2007) · Biology of Reproduction · doi:10.1093/biolreprod/77.s1.98
Metadata
- Authors
- Conover, C. A., Oxvig, C., Overgaard, M. T., Christiansen, M., & Giudice, L. C.
- Affiliations
- Mayo Clinic (US)
- Aarhus University (DK)
- Statens Serum Institut (DK)
- Stanford Medicine (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1999-12
- Volume
- 84
- Issue
- 12
- Pages
- 4742-4745
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2051842303
- Cited by
- 120
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD031579, HD 31579-05)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- IGFBP-4, PAPP-A, follicular fluid, granulosa cells, folliculogenesis, follicular atresia
- MeSH terms
- Edetic Acid, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Female, Fertilization in Vitro, Fibroblasts, Humans, Metalloendopeptidases, Phenanthrolines, Pregnancy-Associated Plasma Protein-A, Follicular Fluid, Culture Media, Conditioned, Insulin-Like Growth Factor Binding Protein 4
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