This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fujiwara, H. Articles by Mori, T. Search for Related Content PubMed PubMed Citation Articles by Fujiwara, H. Articles by Mori, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL PROGESTERONE

Laminin Suppresses Progesterone Production by Human Luteinizing Granulosa Cells via Interaction with Integrin ₆ß₁¹

Department of Gynecology and Obstetrics, Faculty of Medicine (H.F., T.H., K.N., S.Y., T.M.), Institute for Virus Research (M.U.), and Chest Disease Research Institute (M.M.), Kyoto University, Sakyo-ku, Kyoto 606–01, Japan

Address all correspondence and requests for reprints to: Hiroshi Fujiwara, M.D., Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606–01, Japan.

We previously raised a murine monoclonal antibody (mAb), OG-1, against human granulosa cells (GC) and reported that human GC express the OG-1 antigen with the highest immunoreactivity during the periovulatory phase. Later, we showed that the OG-1 antigen is identical to human integrin ₆, and that human GC express integrin ₆ß₁, but not ₆ß₄.

In the present study, we examined the expression of laminin (LN), the ligand for integrin ₆ß₁. Flow cytometry showed that LN was bound to the cell surface of some GC obtained from preovulatory follicles of patients undergoing in vitro fertilization. Immunohistochemistry showed that LN was detected between luteinizing GC in the early corpora lutea.

To examine the effect of LN on steroidogenesis by human luteinizing GC, GC obtained from patients undergoing in vitro fertilization were cultured on mouse LN-coated or noncoated plastic dishes in medium containing 5% FCS for 24 h. In the absence or presence of hCG (1 IU/mL), GC cultured on LN-coated dishes produced 0.70- and 0.67-fold less progesterone than those on noncoated dishes, respectively (P < 0.05).

We examined the effect of the interaction of integrin ₆ß₁ and LN on steroidogenesis by human luteinizing GC. We cultured GC with 5 µg/mL of the anti-₆ mAb GoH3, which inhibits the interaction between human integrin ₆ß₁ and mouse LN, or with a control rat mAb (TER199) on mouse LN-coated dishes in serum-free medium for 24 h. In the absence or presence of hCG (1 IU/mL), GC cultured with GoH3 produced 1.97- and 1.94-fold more progesterone than the control cells (P < 0.01 and P < 0.05, respectively). In contrast, when GC were cultured on dishes coated with type IV collagen, progesterone production was not enhanced by GoH3. Furthermore, the anti-₆ mAb OG-1, which does not inhibit the interaction between integrin ₆ß₁ and LN, had no effect on the progesterone production by GC cultured on LN.

These results indicate that LN suppresses the luteinization of human luteinizing GC via integrin ₆ß₁ and that integrin ₆ß₁ regulates the luteinization of human GC during the periovulatory phase.

This article has been cited by other articles:

				T. Adriaenssens, C. Mazoyer, I. Segers, S. Wathlet, and J. Smitz Differences in Collagen Expression in Cumulus Cells after Exposure to Highly Purified Menotropin or Recombinant Follicle-Stimulating Hormone in a Mouse Follicle Culture Model Biol Reprod, May 1, 2009; 80(5): 1015 - 1025. [Abstract] [Full Text] [PDF]

				K. Furukawa, H. Fujiwara, Y. Sato, B.-X. Zeng, H. Fujii, S. Yoshioka, E. Nishi, and T. Nishio Platelets Are Novel Regulators of Neovascularization and Luteinization during Human Corpus Luteum Formation Endocrinology, July 1, 2007; 148(7): 3056 - 3064. [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]

				I. Virtanen, M. Korhonen, N. Petajaniemi, T. Karhunen, L.-E. Thornell, L. M. Sorokin, and Y. T. Konttinen Laminin Isoforms in Fetal and Adult Human Adrenal Cortex J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4960 - 4966. [Abstract] [Full Text] [PDF]

				M. Egawa, S. Yoshioka, T. Higuchi, Y. Sato, K. Tatsumi, H. Fujiwara, and S. Fujii Ephrin B1 Is Expressed on Human Luteinizing Granulosa Cells in Corpora Lutea of the Early Luteal Phase: The Possible Involvement of the B Class Eph-Ephrin System during Corpus Luteum Formation J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4384 - 4392. [Abstract] [Full Text] [PDF]

				K. Kosaka, H. Fujiwara, K. Tatsumi, S. Yoshioka, Y. Sato, H. Egawa, T. Higuchi, T. Nakayama, M. Ueda, M. Maeda, et al. Human Chorionic Gonadotropin (HCG) Activates Monocytes to Produce Interleukin-8 via a Different Pathway from Luteinizing Hormone/HCG Receptor System J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5199 - 5208. [Abstract] [Full Text] [PDF]

				K. H. Burns, G. E. Owens, J. M. Fernandez, J. H. Nilson, and M. M. Matzuk Characterization of Integrin Expression in the Mouse Ovary Biol Reprod, September 1, 2002; 67(3): 743 - 751. [Abstract] [Full Text] [PDF]

				W. Qin, S. G. Rane, and E. K. Asem Basal lamina of ovarian follicle regulates an inward Cl- current in differentiated granulosa cells Am J Physiol Cell Physiol, January 1, 2002; 282(1): C34 - C48. [Abstract] [Full Text] [PDF]

				E. K. Asem, W. Qin, and S. G. Rane Effect of basal lamina of ovarian follicle on T- and L-type Ca2+ currents in differentiated granulosa cells Am J Physiol Endocrinol Metab, January 1, 2002; 282(1): E184 - E196. [Abstract] [Full Text] [PDF]

				B. D. Murphy Models of Luteinization Biol Reprod, July 1, 2000; 63(1): 2 - 11. [Abstract] [Full Text]

				E. Alexopoulos, J. Shahid, H.Z. Ongley, and M.C. Richardson Luteinized human granulosa cells are associated with endogenous basement membrane-like components in culture Mol. Hum. Reprod., April 1, 2000; 6(4): 324 - 330. [Abstract] [Full Text] [PDF]

				K. R. Park, T. Inoue, M. Ueda, T. Hirano, T. Higuchi, M. Maeda, I. Konishi, H. Fujiwara, and S. Fujii CD9 is expressed on human endometrial epithelial cells in association with integrins {alpha}6, {alpha}3 and {beta}1 Mol. Hum. Reprod., March 1, 2000; 6(3): 252 - 257. [Abstract] [Full Text] [PDF]

				T. Higuchi, H. Fujiwara, S. Yamada, K. Tatsumi, N. Kataoka, K. Itoh, M. Maeda, J. Fujita, and S. Fujii Co-expression of integrin-associated protein (IAP/CD47) and its ligand thrombospondin-1 on human granulosa and large luteal cells Mol. Hum. Reprod., October 1, 1999; 5(10): 920 - 926. [Abstract] [Full Text] [PDF]

				S. Yamada, H. Fujiwara, T. Honda, T. Higuchi, T. Nakayama, T. Inoue, M. Maeda, and S. Fujii Human granulosa cells express integrin {alpha}2 and collagen type IV: possible involvement of collagen type IV in granulosa cell luteinization Mol. Hum. Reprod., July 1, 1999; 5(7): 607 - 617. [Abstract] [Full Text] [PDF]

				Y. Takao, H. Fujiwara, S. Yamada, T. Hirano, M. Maeda, S. Fujii, and M. Ueda CD9 is expressed on the cell surface of human granulosa cells and associated with integrin {alpha}6ß1 Mol. Hum. Reprod., April 1, 1999; 5(4): 303 - 310. [Abstract] [Full Text] [PDF]