HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Hughes, S C C. Articles by Holly, J M P Search for Related Content PubMed PubMed Citation Articles by Hughes, S C C. Articles by Holly, J M P

The IGFs are believed to play an important role in the regulation of steroidogenesis and follicular maturation in the human ovary. The activities of the IGFs are regulated by a family of binding proteins (IGFBPs) which are subject to a number of potential post-translational modifications. The aim of this study was to investigate both the production and modification of the IGFBPs in follicular fluid and in medium conditioned by granulosa cells and theca from individual follicles at different stages of maturation.

In follicular fluid from healthy, dominant follicles there was an increase in the amount of IGFBP-2, -3 and -4 present as lower molecular weight forms (23 kDa, 29 kDa and 16·5 kDa respectively) in comparison to that seen in atretic follicles from the same ovary. Furthermore for IGFBP-4, this fragmentation was confirmed to be attributable to the presence of a specific protease which could be inhibited not only by the addition of metal ion chelators or serine protease inhibitors, but also by the addition of other recombinant unsaturated IGFBPs, particularly IGFBP-3. IGF-I did not modulate the activity of the IGFBP-4 protease in solution but was able to prevent the inhibition seen with IGFBP-3.

Analysis of granulosa cell conditioned medium from the same series of healthy and atretic follicles revealed that IGFBP-2 and -4 were the predominant IGFBPs with no fragments seen on immunoblotting. In contrast, IGFBP-3 in conditioned medium from theca of atretic follicles was always found as an intact doublet, but was found partially fragmented (30 and 32 kDa) in medium conditioned by theca from healthy, dominant follicles with the proportion of IGFBP-3 in this lower molecular weight or fragmented doublet increasing with follicular maturation. A similar situation was also found for IGFBP-4 with the progressive increase in the amount of the 15 and 16·5 kDa fragments. IGFBP-2 was always found to be intact. Finally, IGFBP production from stroma explants was also examined. This revealed a wide variation in IGFBP pattern between different ovaries, although there was a remarkable degree of consistency between different stroma explant cultures from the same ovary. Immunoblotting for IGFBP-3 revealed that, where present, it existed as both an intact and a lower molecular weight doublet and that IGFBP-2 was again always found to be intact.

In conclusion we have demonstrated alterations in the proteolytic modification of the IGFBPs which differ in the various follicular compartments and are closely linked to the stage of follicular development.

Journal of Endocrinology (1997) 154, 35–43

This article has been cited by other articles:

				P. M. Yamada and K.-W. Lee Perspectives in mammalian IGFBP-3 biology: local vs. systemic action Am J Physiol Cell Physiol, May 1, 2009; 296(5): C954 - C976. [Abstract] [Full Text] [PDF]

				P. Monget, S. Mazerbourg, T. Delpuech, M.-C. Maurel, S. Maniere, J. Zapf, G. Lalmanach, C. Oxvig, and M. T. Overgaard Pregnancy-Associated Plasma Protein-A Is Involved in Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) Proteolytic Degradation in Bovine and Porcine Preovulatory Follicles: Identification of Cleavage Site and Characterization of IGFBP-2 Degradation Biol Reprod, January 1, 2003; 68(1): 77 - 86. [Abstract] [Full Text] [PDF]

				R. J. Wright, J. M.P. Holly, R. Galea, M. Brincat, and H. D. Mason Insulin-Like Growth Factor (IGF)-Independent Effects of IGF Binding Protein-4 on Human Granulosa Cell Steroidogenesis Biol Reprod, September 1, 2002; 67(3): 776 - 781. [Abstract] [Full Text] [PDF]

				P. Froment, D. Seurin, S. Hembert, J. E. Levine, C. Pisselet, D. Monniaux, M. Binoux, and P. Monget Reproductive Abnormalities in Human IGF Binding Protein-1 Transgenic Female Mice Endocrinology, May 1, 2002; 143(5): 1801 - 1808. [Abstract] [Full Text] [PDF]

				S. Mazerbourg, M. T. Overgaard, C. Oxvig, M. Christiansen, C. A. Conover, I. Laurendeau, M. Vidaud, G. Tosser-Klopp, J. Zapf, and P. Monget Pregnancy-Associated Plasma Protein-A (PAPP-A) in Ovine, Bovine, Porcine, and Equine Ovarian Follicles: Involvement in IGF Binding Protein-4 Proteolytic Degradation and mRNA Expression During Follicular Development Endocrinology, December 1, 2001; 142(12): 5243 - 5253. [Abstract] [Full Text] [PDF]

				S. Mazerbourg, J. Zapf, R. S. Bar, D. R. Brigstock, and P. Monget 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, August 1, 2000; 63(2): 390 - 400. [Abstract] [Full Text]

				S. Mazerbourg, J. Zapf, R. S. Bar, D. R. Brigstock, C. Lalou, M. Binoux, and P. Monget Insulin-Like Growth Factor Binding Protein-4 Proteolytic Degradation in Ovine Preovulatory Follicles: Studies of Underlying Mechanisms Endocrinology, September 1, 1999; 140(9): 4175 - 4184. [Abstract] [Full Text]

				L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice The Insulin-Related Ovarian Regulatory System in Health and Disease Endocr. Rev., August 1, 1999; 20(4): 535 - 582. [Abstract] [Full Text] [PDF]