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Vertebrate reproductive science and technology
RESEARCH ARTICLE

Insulin-like growth factor binding proteins in follicular fluid from morphologically distinct healthy and atretic bovine antral follicles

H. F. Irving-Rodgers A , K. D. Catanzariti A , M. Master B , P. A. Grant A , P. C. Owens A and R. J. Rodgers A C
+ Author Affiliations
- Author Affiliations

A Department of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia.

B Department of Medicine, Flinders University, Bedford Park, SA 5042, Australia.

C To whom correspondence should be addressed. email: ray.rodgers@adelaide.edu.au

Reproduction, Fertility and Development 15(4) 241-248 https://doi.org/10.1071/RD03008
Submitted: 5 February 2003  Accepted: 24 June 2003   Published: 13 August 2003

Abstract

In bovine follicles 2–5 mm in diameter, two morphologically distinct types of healthy follicles and two types of atretic follicles have been described recently. Healthy follicles either have columnar basal granulosa cells with follicular basal lamina composed of many layers or ‘loops’ or they have rounded basal cells with a conventional single-layered, aligned follicular basal lamina. In atretic follicles, cell death either commences at the basal layer and progresses to the antrum (basal atresia) with macrophage penetration of the membrana granulosa or death progresses from the antrum in a basal direction (antral atresia). Little is known about how these different phenotypes develop. To determine whether insulin-like growth factor binding protein (IGFBP) levels in follicular fluid differ between these different types of follicles, we measured IGFBP levels in fluids from these follicles. A total of 61 follicles were assessed by light microscopy and characterized by morphological analysis as either healthy, with columnar or rounded basal granulosa cells, or as undergoing antral or basal atresia. The IGFBP concentration in the follicular fluid of individual follicles from the four groups (n = 12–20 per group) was identified by Western ligand blots using 125I-insulin-like growth factor (IGF)-II as a probe. Insulin-like growth factor binding proteins 2, 3 (44 and 40 kDa), 4 (glycosylated and non-glycosylated) and 5 were observed. The levels (per volume of fluid) of IGFBPs 2, 4 and 5 were greater in atretic follicles than in healthy follicles. However, there were no statistical differences in levels of each IGFBP between either the two types of healthy follicle or between the two types of atretic follicles. Thus, IGFBP levels are not related to the different types of healthy or atretic follicles.

Extra keywords: cattle


Acknowledgments

This research was supported by the National Health and Medical Research Council of Australia, Adelaide University and the Research Council of Australia.


References

Angelloz-Nicoud, P. , and Binoux, M. (1995). Autocrine regulation of cell proliferation by the insulin-like growth factor (IGF) and IGF binding protein-3 protease system in a human prostate carcinoma cell line (PC-3) Endocrinology 136, 5485–92.
PubMed |

Armstrong, D. G. , Baxter, G. , Gutierrez, C. G. , Hogg, C. O. , Glazyrin, A.L. , Campbell, B. K. , Bramley, T. A. , and Webb, R. (1998). Insulin-like growth factor binding protein-2 and -4 messenger ribonucleic acid expression in bovine ovarian follicles: effect of gonadotropins and developmental status Endocrinology 139, 2146–54.
PubMed |

Baranao, J. L. , and Hammond, J. M. (1984). Comparative effects of insulin and insulin-like growth factors on DNA synthesis and differentiation of porcine granulosa cells Biochem. Biophys. Res. Commun. 124, 484–90.
PubMed |

Cataldo, N. A. , and Giudice, L. C. (1992). Insulin-like growth factor binding protein profiles in human ovarian follicular fluid correlate with follicular functional status J. Clin. Endocrinol. Metab. 74, 821–9.
PubMed |

Chandrasekher, Y. A. , Van Dessel, H. J. , Fauser, B. C. , and Giudice, L. C. (1995). Estrogen- but not androgen-dominant human ovarian follicular fluid contains an insulin-like growth factor binding protein-4 protease J. Clin. Endocrinol. Metab. 80, 2734–9.
PubMed |

Charlton, S. T. , Cameron, B. J. , Glimm, D. R. , Foxcroft, G. R. , and Kennelly, J. J. (1993). Insulin like growth factor I gene expression in porcine ovarian tisssue Can. J. Anim. Sci. 73, 253–7.


Clemmons, D. R. (1998). Role of insulin-like growth factor binding proteins in controlling IGF actions Mol. Cell. Endocrinol. 140, 19–24.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Cohen, P. , Peehl, D. M. , Lamson, G. , and Rosenfeld, R. G. (1991). Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells J. Clin. Endocrinol. Metab. 73, 401–7.
PubMed |

Cohen, P. , Lamson, G. , Okajima, T. , and Rosenfeld, R. G. (1993). Transfection of the human IGFBP-3 gene into BALB/c fibroblasts: a model for the cellular functions of IGFBPs Growth Regul. 3, 23–6.
PubMed |

Conover, C. A. , and Kiefer, M. C. (1993). Regulation and biological effect of endogenous insulin-like growth factor binding protein-5 in human osteoblastic cells J. Clin. Endocrinol. Metab. 76, 1153–9.
PubMed |

Echternkamp, S. E. , Spicer, L. J. , Gregory, K. E. , Canning, S. F. , and Hammond, J. M. (1990). Concentrations of insulin-like growth factor-I in blood and ovarian follicular fluid of cattle selected for twins Biol. Reprod. 43, 8–14.
PubMed |

Echternkamp, S. E. , Spicer, L. J. , Klindt, J. , Vernon, R. K. , Yen, J. T. , and Buonomo, F. C. (1994a). Administration of porcine somatotropin by a sustained-release implant: effect on follicular growth, concentrations of steroids and insulin-like growth factor I, and insulin-like growth factor binding protein activity in follicular fluid of control, lean, and obese gilts J. Anim. Sci. 72, 2431–40.
PubMed |

Echternkamp, S. E. , Howard, H. J. , Roberts, A. J. , Grizzle, J. , and Wise, T. (1994b). Relationships among concentrations of steroids, insulin-like growth factor-I, and insulin-like growth factor binding proteins in ovarian follicular fluid of beef cattle Biol. Reprod. 51, 971–81.
PubMed |

el-Roeiy, A. , Chen, X. , Roberts, V. J. , Shimasakai, S. , Ling, N. , LeRoith, D. , Roberts, C. T. , and Yen, S. S. (1994). Expression of the genes encoding the insulin-like growth factors (IGF-I and II), the IGF and insulin receptors, and IGF-binding proteins-1–6 and the localization of their gene products in normal and polycystic ovary syndrome ovaries J. Clin. Endocrinol. Metab. 78, 1488–96.
PubMed |

Erickson, G. F. , and Danforth, D. R. (1995). Ovarian control of follicle development Am. J. Obstet. Gynecol. 172, 736–47.
PubMed |

Erickson, G. F. , Nakatani, A. , Ling, N. , and Shimasaki, S. (1992a). Localization of insulin-like growth factor-binding protein-5 messenger ribonucleic acid in rat ovaries during the estrous cycle Endocrinology 130, 1867–78.
PubMed |

Erickson, G. F. , Nakatani, A. , Ling, N. , and Shimasaki, S. (1992b). Cyclic changes in insulin-like growth factor-binding protein-4 messenger ribonucleic acid in the rat ovary Endocrinology 130, 625–36.
PubMed |

Funston, R. N. , Seidel, G. E. , Klindt, J. , and Roberts, A. J. (1996). Insulin-like growth factor I and insulin-like growth factor-binding proteins in bovine serum and follicular fluid before and after the preovulatory surge of luteinizing hormone Biol. Reprod. 55, 1390–6.
PubMed |

Geisthovel, F. , Moretti-Rojas, I. , Asch, R. H. , and Rojas, F. J. (1989). Expression of insulin-like growth factor-II (IGF-II) messenger ribonucleic acid (mRNA), but not IGF-I mRNA, in human preovulatory granulosa cells Hum. Reprod. 4, 899–902.
PubMed |

Glister, C. , Groome, N. P. , and Knight, P. G. (2003). Oocyte-mediated suppression of follicle-stimulating hormone- and insulin-like growth factor-induced secretion of steroids and inhibin-related proteins by bovine granulosa cells in vitro: possible role of transforming growth factor alpha Biol. Reprod. 68, 758–65.
PubMed |

Gong, J. G. , McBride, D. , Bramley, T. A. , and Webb, R. (1993). Effects of recombinant bovine somatotrophin, insulin-like growth factor-I and insulin on the proliferation of bovine granulosa cells in vitro.  J. Endocrinol. 139, 67–75.
PubMed |

Gong, J. G. , McBride, D. , Bramley, T. A. , and Webb, R. (1994). Effects of recombinant bovine somatotrophin, insulin-like growth factor-I and insulin on bovine granulosa cell steroidogenesis in vitro.  J. Endocrinol. 143, 157–64.
PubMed |

Hughes, S. C. , Mason, H. D. , Franks, S. , and Holly, J. M. (1997). Modulation of the insulin like growth factor binding proteins by follicle size in the human ovary J. Endocrinol. 154, 35–43.
PubMed |

Imai, Y. , Busby, W. H. Jr , Smith, C. E. , Clarke, J. B. , Garmong, A. J. , Horwitz, G. D. , Rees, C. , and Clemmons, D. R. (1997). Protease-resistant form of insulin-like growth factor-binding protein 5 is an inhibitor of insulin-like growth factor-I actions on porcine smooth muscle cells in culture Clin. Invest. 100, 2596–605.


Irving-Rodgers, H. F. , and Rodgers, R. J. (2000). Ultrastructure of the basal lamina of bovine ovarian follicles and its relationship to the membrana granulosa J. Reprod. Fertil. 118, 221–8.
PubMed |

Irving-Rodgers, H. F. , van Wezel, I. L. , Mussard, M. L. , Kinder, J. E. , and Rodgers, R. J. (2001). Atresia revisited: two basic patterns of atresia of bovine antral follicles Reproduction 122, 761–75.
PubMed |

Iwashita, M. , Kudo, Y. , Yoshimura, Y. , Adachi, T. , Katayama, E. , and Takeda, Y. (1996). Physiological role of insulin-like-growth-factor-binding protein-4 in human folliculogenesis Horm. Res. 46, 31–6.
PubMed |

Jones, J. I. , and Clemmons, D. R. (1995). Insulin-like growth factors and their binding proteins: biological actions Endocr. Rev. 16, 3–34.
PubMed |

Jones, J. I. , Gockerman, A. , Busby, W. H. Jr , Camacho-Hubner, C. , and Clemmons, D. R. (1993). Extracellular matrix contains insulin-like growth factor binding protein-5: potentiation of the effects of IGF-I J. Cell Biol. 121, 679–87.
PubMed |

Jung, Y. , Miura, M. , and Yuan, J. (1996). Suppression of interleukin-1 beta-converting enzyme-mediated cell death by insulin-like growth factor J. Biol. Chem. 271, 5112–17.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Kelley, R. L. , Jungst, S. B. , Spencer, T. E. , Owsley, W. F. , Rahe, C. H. , and Mulvaney, D. R. (1995). Maternal treatment with somatotropin alters embryonic development and early postnatal growth of pigs Domest. Anim. Endocrinol. 12, 83–94.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Lavranos, T. C. , O'Leary, P. C. , and Rodgers, R. J. (1996). Effects of insulin-like growth factors and binding protein 1 on bovine granulosa cell division in anchorage-independent culture J. Reprod. Fertil. 107, 221–8.
PubMed |

Lavranos, T. C. , Mathis, J. M. , Latham, S. E. , Kalionis, B. , Shay, J. W. , and Rodgers, R. J. (1999). Evidence for ovarian granulosa stem cells: telomerase activity and localisation of the telomerase RNA component in bovine ovarian follicles Biol. Reprod. 61, 358–66.
PubMed |

Liu, L. , Delbe, J. , Blat, C. , Zapf, J. , and Harel, L. (1992). Insulin-like growth factor binding protein (IGFBP-3), an inhibitor of serum growth factors other than IGF-I and -II J. Cell Physiol. 153, 15–21.
PubMed |

Mason, H. D. , Margara, R. , Winston, R. M. , Seppala, M. , Koistinen, R. , and Franks, S. (1993). Insulin-like growth factor-I (IGF-I) inhibits production of IGF-binding protein-1 while stimulating estradiol secretion in granulosa cells from normal and polycystic human ovaries J. Clin. Endocrinol. Metab. 76, 1275–9.
PubMed |

Mason, H. D. , Cwyfan-Hughes, S. , Holly, M. P. , and Franks, S. (1998). Potent inhibition of human ovarain steroidogenesis by insulin like growth factor binding protein 4 J. Clin. Endocrinol. Metab. 83, 284–7.
PubMed |

Mihm, M. , Austin, E. J. , Good, T. E. M. , Ireland, J. L. H. , Knight, P. G. , Roche, J. F. , and Ireland, J. J. (2000). Identification of potential intrafollicular factors involved in selection of dominant follicles in heifers Biol. Reprod. 63, 811–19.
PubMed |

Mondschein, J. S. , Etherton, T. D. , and Hammond, J. M. (1991). Characterization of insulin-like growth factor-binding proteins of porcine ovarian follicular fluid Biol. Reprod. 44, 315–20.
PubMed |

Monget, P. , Monniaux, D. , and Durand, P. (1989). Localization, characterization, and quantification of insulin-like growth factor-I-binding sites in the ewe ovary Endocrinology 125, 2486–93.
PubMed |

Monget, P. , Monniaux, D. , Pisselet, C. , and Durand, P. (1993). Changes in insulin-like growth factor-I (IGF-I), IGF-II, and their binding proteins during growth and atresia of ovine ovarian follicles Endocrinology 132, 1438–46.
PubMed |

Murphy, L. J. , Bell, G. I. , and Friesen, H. G. (1987). Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat Endocrinology 120, 1279–82.
PubMed |

Nicholas, B. , Scougall, R. K. , Armstrong, D. G. , and Webb, R. (2002). Changes in insulin-like growth factor binding protein (IGFBP) isoforms during bovine follicular development Reproduction 124, 439–46.
PubMed |

Nissley, S. P. , and Rechler, M. M. (1986). Insulin-like growth factor (IGF)/somatomedin receptor subtypes: structure, function, and relationships to insulin receptors and IGF carrier proteins Horm. Res. 24, 152–9.
PubMed |

Rees, C. , Clemmons, D. R. , Horvitz, G. D. , Clarke, J. B. , and Busby, W. H. (1998). A protease-resistant form of insulin-like growth factor (IGF) binding protein 4 inhibits IGF-1 actions Endocrinology 139, 4182–8.
PubMed |

Rivera, G. M. , Chandrasekher, Y. A. , Evans, A. C. , Giudice, L. C. , and Fortune, J. E. (2001). A potential role for insulin-like growth factor binding protein-4 proteolysis in the establishment of ovarian follicular dominance in cattle Biol. Reprod. 65, 102–11.
PubMed |

Rodgers, R. J. , Irving-Rodgers, H. F. , van Wezel, I. L. , Krupa, M. , and Lavranos, T. C. (2001). Dynamics of the membrana granulosa during expansion of the ovarian follicular antrum Mol. Cell. Endocrinol. 171, 41–8.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Rohan, R. M. , Ricciarelli, E. , Kiefer, M. C. , Resnick, C. E. , and Adashi, E. Y. (1993). Rat ovarian insulin-like growth factor-binding protein-6: a hormonally regulated theca-interstitial-selective species with limited antigonadotropic activity Endocrinology 132, 2507–12.
PubMed |

Samaras, S. E. , Hagen, D. R. , Bryan, K. A. , Mondschein, J. S. , Canning, S. F. , and Hammond, J. M. (1994). Effects of growth hormone and gonadotropin on the insulin-like growth factor system in the porcine ovary Biol. Reprod. 50, 178–86.
PubMed |

San Roman, G. A. , and Magoffin, D. A. (1992). Insulin-like growth factor binding proteins in ovarian follicles from women with polycystic ovarian disease: cellular source and levels in follicular fluid J. Clin. Endocrinol. Metab. 75, 1010–16.
PubMed |

Savion, N. , Liu, G. M. , Laherty, R. , and Gospodarowicz, D. (1981). Factors controlling proliferation and progesterone production by bovine granulosa cells in serum free medium Endocrinology 109, 409–20.
PubMed |

Schmid, C. , Rutishauser, J. , Schlapfer, I. , Froesch, E. R. , and Zapf, J. (1991). Intact but not truncated insulin-like growth factor binding protein-3 (IGFBP-3) blocks IGF I-induced stimulation of osteoblasts: control of IGF signalling to bone cells by IGFBP-3-specific proteolysis? Biochem. Biophys. Res.Commun. 179, 579–85.
PubMed |

Schuller, A. G. , Lindenbergh-Kortleve, D. J. , Pache, T. D. , Zwarthoff, E. C. , Fa, B. C. , and Drop, S. L. (1993). Insulin-like growth factor binding protein-2, 28 kDa and 24 kDa insulin-like growth factor binding protein levels are decreased in fluid of dominant follicles, obtained from normal and polycystic ovaries Regul. Pept. 48, 157–63.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Shimasaki, S. , Shimonaka, M. , Zhang, H. P. , and Ling, N. (1991). Identification of five different insulin-like growth factor binding proteins (IGFBPs) from adult rat serum and molecular cloning of a novel IGFBP-5 in rat and human J. Biol. Chem. 266, 10 646–53.


Sokal, R. R., and  Rohlf, F. J. (1969). Biometry. The Principles and Practice of Statistics in Biological Research. (W. H. Freeman and Co.: San Francisco.)

Spicer, L. J. , and Chamberlain, C. S. (1998). Influence of cortisol on insulin- and insulin-like growth factor I (IGF-I)-induced steroid production and on IGF-I receptors in cultured bovine granulosa cells and thecal cells Endocrine 9, 153–61.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Spicer, L. J. , and Echternkamp, S. E. (1995). The ovarian insulin and insulin-like growth factor system with an emphasis on domestic animals Domest. Anim. Endocrinol. 12, 223–45.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Spicer, L. J. , Alpizar, E. , and Echternkamp, S. E. (1993). Effects of insulin, insulin-like growth factor I, and gonadotropins on bovine granulosa cell proliferation, progesterone production, estradiol production, and (or) insulin-like growth factor I production in vitro.  J. Anim. Sci. 71, 1232–41.
PubMed |

Spicer, L. J. , Chamberlain, C. S. , and Morgan, G. L. (2001). Proteolysis of insulin-like growth factor binding proteins during preovulatory follicular development in cattle Domest. Anim. Endocrinol. 21, 1–15.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Spicer, L. J. , Chamberlain, C. S. , and Maciel, S. M. (2002). Influence of gonadotropins on insulin- and insulin-like growth factor-I (IGF-I)-induced steroid production by bovine granulosa cells Domest. Anim. Endocrinol. 22, 237–54.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Steinkampf, M. P. , Mendelson, C. R. , and Simpson, E. R. (1988). Effects of epidermal growth factor and insulin-like growth factor I on the levels of mRNA encoding aromatase cytochrome P-450 of human ovarian granulosa cells Mol. Cell Endocrinol. 59, 93–9.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Stewart, R. E. , Spicer, L. J. , Hamilton, T. D. , Keefer, B. E. , Dawson, L. J. , Morgan, G. L. , and Echternkamp, S. E. (1996). Levels of insulin-like growth factor (IGF) binding proteins, luteinizing hormone and IGF-I receptors, and steroids in dominant follicles during the first follicular wave in cattle exhibiting regular estrous cycles Endocrinology 137, 2842–50.
PubMed |

Valentinis, B. , Bhala, A. , DeAngelis, T. , Baserga, R. , and Cohen, P. (1995). The human insulin-like growth factor (IGF) binding protein-3 inhibits the growth of fibroblasts with a targeted disruption of the IGF-I receptor gene Mol. Endocrinol. 9, 361–7.
PubMed |

van Wezel, I. L. , Krupa, M. , and Rodgers, R. J. (1999). Development of the membrana granulosa of bovine antral follicles: structure, location of mitosis and pyknosis, and immunolocalization of involucrin and vimentin Reprod. Fertil. Dev. 11, 37–48.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Veldhuis, J. D. , and Furlanetto, R. W. (1985). Trophic actions of human somatomedin C/insulin-like growth factor I on ovarian cells: in vitro studies with swine granulosa cells Endocrinology 116, 1235–42.
PubMed |

Zhou, J. , and Bondy, C. (1993). Anatomy of the human ovarian insulin-like growth factor system Biol. Reprod. 48, 467–82.
PubMed |