This study aimed to determine the physiological role of laminin (LN) and its receptor, alpha(6)beta(1) integrin, in controlling the functions of granulosa cells (GC) during follicular development in sheep ovary. Immunohistochemistry experiments showed the presence of increasing levels of LN (P<0.0001), and high levels of mature alpha(6)beta(1) integrin in GC layers of healthy antral follicles during the follicular and the preovulatory phases of the estrous cycle. In vitro, the addition of a function-blocking antibody raised against alpha(6) subunit (anti-alpha(6) IgG) to the medium of ovine GC cultured on LN impaired cell spreading (P<0.0001), decreased the proliferation rate (P<0.05) and increased the apoptosis rate (P<0.05). Furthermore, addition of anti-alpha(6) IgG enhanced estradiol (E2) secretion by GC in the presence or absence of follicle-stimulating hormone (FSH), luteinizing hormone or insulin-like growth factor-I in culture medium (P<0.0001), and inhibited progesterone (P4) secretion in basal conditions or in the presence of low (0.5 ng/ml) FSH concentrations only (P<0.0001). The anti-alpha(6) IgG effect was specific to an interaction of LN with alpha(6)beta(1) integrin since it was ineffective on GC cultured on heat-denatured LN, RGD (arginine-glycine-aspartic acid) peptides and non-coated substratum. Hence, this study established that alpha(6)beta(1) integrin 1) was expressed in GC of antral follicles, 2) mediated the actions of LN on survival, proliferation and steroidogenesis of GC, and 3) was able to dramatically modulate P4 and E2 secretion by GC in vitro. It is suggested that during the follicular and the preovulatory phases of the estrous cycle, the increasing levels of LN in GC of large antral follicles might support their final development to ovulation.

This article has been cited by other articles:

				T. K. Woodruff and L. D. Shea The Role of the Extracellular Matrix in Ovarian Follicle Development Reproductive Sciences, December 1, 2007; 14(8_suppl): 6 - 10. [Abstract] [PDF]

				M. Otis, S. Campbell, M. D Payet, and N. Gallo-Payet Expression of extracellular matrix proteins and integrins in rat adrenal gland: importance for ACTH-associated functions J. Endocrinol., June 1, 2007; 193(3): 331 - 347. [Abstract] [Full Text] [PDF]

				M. Pannetier, S. Fabre, F. Batista, A. Kocer, L. Renault, G. Jolivet, B. Mandon-Pepin, C. Cotinot, R. Veitia, and E. Pailhoux FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development. J. Mol. Endocrinol., June 1, 2006; 36(3): 399 - 413. [Abstract] [Full Text] [PDF]

				S. K. Saha, P. Ghosh, A. Konar, S. Bhattacharya, and S. S. Roy Differential Expression of Procollagen Lysine 2-Oxoglutarate 5-Deoxygenase and Matrix Metalloproteinase Isoforms in Hypothyroid Rat Ovary and Disintegration of Extracellular Matrix Endocrinology, July 1, 2005; 146(7): 2963 - 2975. [Abstract] [Full Text] [PDF]

				A Pierre, C Pisselet, J Dupont, B Mandon-Pepin, D Monniaux, P Monget, and S Fabre Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells J. Mol. Endocrinol., December 1, 2004; 33(3): 805 - 817. [Abstract] [Full Text] [PDF]

				P. Froment, S. Fabre, J. Dupont, C. Pisselet, D. Chesneau, B. Staels, and P. Monget Expression and Functional Role of Peroxisome Proliferator-Activated Receptor-{gamma} in Ovarian Folliculogenesis in the Sheep Biol Reprod, November 1, 2003; 69(5): 1665 - 1674. [Abstract] [Full Text] [PDF]

				M. J. Calzada, J. M. Sipes, H. C. Krutzsch, P. D. Yurchenco, D. S. Annis, D. F. Mosher, and D. D. Roberts Recognition of the N-terminal Modules of Thrombospondin-1 and Thrombospondin-2 by {alpha}6{beta}1 Integrin J. Biol. Chem., October 17, 2003; 278(42): 40679 - 40687. [Abstract] [Full Text] [PDF]

				G. P. Pidgeon, K. Tang, Y. L. Cai, E. Piasentin, and K. V. Honn Overexpression of Platelet-type 12-Lipoxygenase Promotes Tumor Cell Survival by Enhancing {alpha}v{beta}3 and {alpha}v{beta}5 Integrin Expression Cancer Res., July 15, 2003; 63(14): 4258 - 4267. [Abstract] [Full Text] [PDF]

				C. Mulligan, J. Rochford, G. Denyer, R. Stephens, G. Yeo, T. Freeman, K. Siddle, and S. O'Rahilly Microarray Analysis of Insulin and Insulin-like Growth Factor-1 (IGF-1) Receptor Signaling Reveals the Selective Up-regulation of the Mitogen Heparin-binding EGF-like Growth Factor by IGF-1 J. Biol. Chem., November 1, 2002; 277(45): 42480 - 42487. [Abstract] [Full Text] [PDF]