The active form of goat insulin-like peptide 3 (INSL3) is a single-chain structure comprising three domains B-C-A, constitutively expressed and secreted by testicular Leydig cells

References

Adham, I.M., Burkhardt, E., Benahmed, M., and Engel, W. (1993). Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells. J. Biol. Chem. 268, 26668–26672.10.1016/S0021-9258(19)74364-6Search in Google Scholar

Anand-Ivell, R.J., Relan, V., Balvers. M., Coiffec-Dorval, I., Fritsch, M., Bathgate, R.A, and Ivell, R. (2006). Expression of the insulin-like peptide 3 (INSL3) hormone-receptor system in the testis. Biol. Reprod. 74, 945–953.10.1095/biolreprod.105.048165Search in Google Scholar PubMed

Anand-Ivell, R., Heng, K., Hafen, B., Setchell, B., and Ivell, R. (2009). Dynamics of INSL3 peptide expression in the rodent testis. Biol. Reprod. 81, 480–487.10.1095/biolreprod.109.077552Search in Google Scholar PubMed

Balvers, M., Spiess, A.N., Domagalski, R., Hunt, N., Kilic, E., Mukhopadhyay, A.K., Hanks, E., Charlton, H.M., and Ivell, R. (1998). Relaxin-like factor expression as a marker of differentiation in the mouse testis and ovary. Endocrinology 139, 2960–2970.10.1210/endo.139.6.6046Search in Google Scholar PubMed

Bogatcheva, N.V., Truong, A., Feng, S., Engel, W., Adham, I.M., and Agoulnik, A.I. (2003). GREAT/LGR8 is the only receptor for insulin-like 3 peptide. Mol. Endocrinol. 17, 2639–2646.10.1210/me.2003-0096Search in Google Scholar PubMed

Büllesbach, E.E. and Schwabe, C. (1995). A novel Leydig cell cDNA-derived protein is a relaxin-like factor. J. Biol. Chem. 270, 16011–16015.10.1074/jbc.270.27.16011Search in Google Scholar PubMed

Büllesbach, E.E. and Schwabe, C. (2002). The primary structure and the disulfide links of the bovine relaxin-like factor (RLF). Biochemistry 41, 274–281.10.1021/bi0117302Search in Google Scholar PubMed

Deveson, S., Forsyth, I.A., and Arendt, J. (1992). Retardation of pubertal development by prenatal long days in goat kids born in autumn. J. Reprod. Fertil. 95, 629–637.10.1530/jrf.0.0950629Search in Google Scholar PubMed

Feng, S., Bogatcheva, N.V., Truong, A., Korchin, B., Bishop, C.E., Klonisch, T., Agoulnik, I.U., and Agoulnik, A.I. (2007). Developmental expression and gene regulation of insulin-like 3 receptor RXFP2 in mouse male reproductive organs. Biol. Reprod. 77, 671–680.10.1095/biolreprod.107.060442Search in Google Scholar PubMed

Ferlin, A. and Foresta, C. (2005). Insulin-like factor 3: a novel circulating hormone of testicular origin in humans. Ann. N. Y. Acad. Sci. 1041, 497–505.10.1196/annals.1282.074Search in Google Scholar PubMed

Filonzi, M., Cardoso, L.C., Pimenta, M.T., Queiróz, D.B., Avellar, M.C., Porto, C.S., and Lazari, M.F. (2007). Relaxin family peptide receptors Rxfp1 and Rxfp2: mapping of the mRNA and protein distribution in the reproductive tract of the male rat. Reprod. Biol. Endocrinol. 5, 29 (12 pages).10.1186/1477-7827-5-29Search in Google Scholar

Gorlov, I.P., Kamat, A., Bogatcheva, N.V., Jones, E., Lamb, D.J., Truong, A., Bishop, C.E., McElreavey, K., and Agoulnik, A.I. (2002). Mutations of the GREAT gene cause cryptorchidism. Hum. Mol. Genet. 11, 2309–2318.10.1093/hmg/11.19.2309Search in Google Scholar

Gustafsson, K., Sultana, T., Zetterström, C.K., Setchell, B.P., Siddiqui, A., Weber, G., and Söder, O. (2002). Production and secretion of interleukin-1alpha proteins by rat testis. Biochem. Biophys. Res. Commun. 297, 492–497.10.1016/S0006-291X(02)02239-8Search in Google Scholar

Halban, P.A. and Irminger, J.C. (1994). Sorting and processing of secretory proteins. Biochem. J. 299, 1–18.10.1042/bj2990001Search in Google Scholar

Hess, H.H., Lees, M.B., and Derr, J.E. (1978). A linear Lowry-Folin assay for both water-soluble and sodium dodecyl sulfate-solubilized proteins. Anal. Biochem. 85, 295–300.10.1016/0003-2697(78)90304-4Search in Google Scholar

Hombach-Klonisch, S., Tetens, F., Kauffold, J., Steger, K., Fischer, B., and Klonisch, T. (1999). Molecular cloning and localization of caprine relaxin-like factor (RLF) mRNA within the goat testis. Mol. Reprod. Dev. 53, 135–141.10.1002/(SICI)1098-2795(199906)53:2<135::AID-MRD2>3.0.CO;2-JSearch in Google Scholar

Hombach-Klonisch, S., Buchmann, J., Sarun, S., Fischer, B., and Klonisch, T. (2000). Relaxin-like factor (RLF) is differentially expressed in the normal and neoplastic human mammary gland. Cancer 89, 2161–2168.10.1002/1097-0142(20001201)89:11<2161::AID-CNCR3>3.0.CO;2-KSearch in Google Scholar

Hombach-Klonisch, S., Schön, J., Kehlen, A., Blottner, S., and Klonisch, T. (2004). Seasonal expression of INSL3 and Lgr8/Insl3 receptor transcripts indicates variable differentiation of Leydig cells in the roe deer testis. Biol. Reprod. 71, 1079–1087.10.1095/biolreprod.103.024752Search in Google Scholar

Hsu, S.Y., Nakabayashi, K., Nishi, S., Kumagai, J., Kudo, M., Sherwood, O.D., and Hsueh, A.J. (2002). Activation of orphan receptors by the hormone relaxin. Science 295, 671–674.10.1126/science.1065654Search in Google Scholar

Ivell, R. and Anand-Ivell, R. (2009). Biology of insulin-like factor 3 in human reproduction. Human Reprod. Update 15, 463–476.10.1093/humupd/dmp011Search in Google Scholar

Ivell, R. and Bathgate, R.A. (2002). Reproductive biology of the relaxin-like factor (RLF/INSL3). Biol. Reprod. 67, 699–705.10.1095/biolreprod.102.005199Search in Google Scholar

Ivell, R., Kotula-Balak, M., Glynn, D., Heng, K., and Anand-Ivell, R. (2011). Relaxin family peptides in the male reproductive system– a critical appraisal. Mol. Hum. Reprod. 17, 71–84.10.1093/molehr/gaq086Search in Google Scholar

Jutras, I., Seidah, N.G., Reudelhuber, T.L., and Brechler, V. (1997). Two activation states of the prohormone convertase PC1 in the secretory pathway. J. Biol. Chem. 272, 15184–15188.10.1074/jbc.272.24.15184Search in Google Scholar

Kato, S., Siqin, Minagawa, I., Aoshima, T., Sagata, D., Konishi, H., Yogo, K., Kawarasaki, T., Sasada, H., Tomogane, H., and Kohsaka, T. (2010). Evidence for expression of relaxin hormone-receptor system in the boar testis. J. Endocrinol. 207, 135–149.10.1677/JOE-10-0149Search in Google Scholar

Kawamura, K., Kumagai, J., Sudo, S., Chun, S., Pisarska, M., Morita, H., Toppari, J., Fu, P., Wade, J.D., Bathgate, R.A., et al. (2004). Paracrine regulation of mammalian oocyte maturation and male germ cell survival. Proc. Natl. Acad. Sci. USA 101, 7323–7328.10.1073/pnas.0307061101Search in Google Scholar

Kelly, R.B. (1985). Pathways of protein secretion in eukaryotes. Science 230, 25–32.10.1126/science.2994224Search in Google Scholar

Klonisch, T., Steger, K., Kehlen, A., Allen, W.R., Froehlich, C., Kauffold, J., Bergmann, M., and Hombach-Klonisch, S. (2003). INSL3 ligand-receptor system in the equine testis. Biol. Reprod. 68, 1975–1981.10.1095/biolreprod.102.008466Search in Google Scholar

Koeva, Y.A., Bakalska, M.V., Atanassova, N.N., and Davidoff, M.S. (2008). INSLF3-LGR8 ligand-receptor system in testes of mature rats after exposure to ethane dimethanesulphonate. Folia Med. (Plovdiv) 50, 37–42.Search in Google Scholar

Kohsaka, T., Sasada, H., and Masaki, J. (1992). Subcellular localization of the antigenic sites of relaxin in the luteal cells of the pregnant rat using an improved immunocytochemical technique. Anim. Reprod. Sci. 29, 123–132.10.1016/0378-4320(92)90026-ASearch in Google Scholar

Kohsaka, T., Sasada, H., and Masaki, J. (1993a). Subcellular localization of the maturation process of relaxin in rat luteal cells during pregnancy as revealed by immunogold labeling. Anim. Reprod. Sci. 34, 159–166.10.1016/0378-4320(93)90074-2Search in Google Scholar

Kohsaka, T., Takahara, H., Sugawara, K., and Tagami, S. (1993b). Endogenous heterogeneity of relaxin and sequence of the major form in pregnant sow ovaries. Biol. Chem. Hoppe Seyler 374, 203–210.10.1515/bchm3.1993.374.1-6.203Search in Google Scholar PubMed

Kumagai, J., Hsu, S.Y., Matsumi, H., Roh, J.S., Fu, P., Wade, J.D., Bathgate, R.A., and Hsueh, A.J. (2002). INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent. J. Biol. Chem. 277, 31283–31286.10.1074/jbc.C200398200Search in Google Scholar

LeRoith, D. and Roberts, C.T. (2003). The insulin-like growth factor system and cancer. Cancer Lett. 195, 127–137.10.1016/S0304-3835(03)00159-9Search in Google Scholar

Lunstra, D.D., Ford, J.J., Christenson, R.K., and Allrich, R.D. (1986). Changes in Leydig cell ultrastructure and function during pubertal development in the boar. Biol. Reprod. 34, 145–158.10.1095/biolreprod34.1.145Search in Google Scholar PubMed

Marriott, D., Gillece-Castro, B., and Gorman, C.M. (1992). Prohormone convertase-1 will process prorelaxin, a member of the insulin family of hormones. Mol. Endocrinol. 6, 1441–1450.Search in Google Scholar

McKinnell, C., Sharpe, R.M., Mahood, K., Hallmark, N., Scott, H., Ivell, R., Staub, C., Jégou, B., Haag, F., Koch-Nolte, F., et al. (2005). Expression of insulin-like factor 3 protein in the rat testis during fetal and postnatal development and in relation to cryptorchidism induced by in utero exposure to di (n-Butyl) phthalate. Endocrinology 146, 4536–4544.10.1210/en.2005-0676Search in Google Scholar PubMed

Minagawa, I., Fukuda, M., Kohriki, H., Shibata, M., Park, E.Y., Kawarasaki, T., and Kohsaka, T. (2012). Relaxin-like factor (RLF)/insulin-like peptide 3 (INSL3) is secreted from testicular Leydig cells as a monomeric protein comprising three domains B-C-A with full biological activity in boars. Biochem. J. 441, 265–273.10.1042/BJ20111107Search in Google Scholar PubMed PubMed Central

Nakayama, K. (1997). Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins. Biochem. J. 327, 625–635.10.1042/bj3270625Search in Google Scholar PubMed PubMed Central

Nef, S. and Parada, L.F. (1999). Cryptorchidism in mice mutant for Insl3. Nature Genetics 22, 295–299.10.1038/10364Search in Google Scholar PubMed

Nielsen, H., Engelbrecht, J., Brunak, S., and von Heijne, G. (1997). Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 10, 1–6.10.1093/protein/10.1.1Search in Google Scholar PubMed

Ogine, T., Kohsaka, T., and Taya, K. (1999). Time-resolved fluoroimmunoassay (TR-FIA) of porcine relaxin. Exp. Clin. Endocrinol. Diabetes 107, 276–280.10.1055/s-0029-1212112Search in Google Scholar PubMed

Rorsman, P. and Renström, E.I. (2003). Insulinn granule dynamics in pancreatic beta cells. Diabetologia 46, 1029–1045.10.1007/s00125-003-1153-1Search in Google Scholar PubMed

Sadeghian, H., Anand-Ivell, R., Balvers, M., Relan, V., and Ivell, R. (2005). Constitutive regulation of the Insl3 gene in rat Leydig cells. Mol. Cell. Endocrinol. 241, 10–20.10.1016/j.mce.2005.03.017Search in Google Scholar

Siqin, Kotani, M., Aoshima, T., Nakai, M., Fuchigami, M., Odanaka, Y., Sugawara, Y., Yogo, K., Nagura, Y., Hamano, K., et al. (2010a). Protein localization of relaxin-like factor in goat testes and its expression pattern during sexual development. Nihon Chikusan Gakkaiho 81, 1–9.10.2508/chikusan.81.1Search in Google Scholar

Siqin, Nakai, M., Hagi, T., Kato, S., Pittia, A.M, Kotani, M., Odanaka, Y., Sugawara, Y., Hamano, K., Yogo, K., et al. (2010b). Partial cDNA sequence of a relaxin-like factor (RLF) receptor, LGR8 and possible existence of the RLF ligand-receptor ststem in goat testes. Anim. Sci. J. 81, 681–686.10.1111/j.1740-0929.2010.00801.xSearch in Google Scholar

Smith, K.J., Wade, J.D., Claasz, A.A., Otvos, L. Jr., Temelcos, C., Kubota, Y., Hutson, J.M., Tregear, G.W., and Bathgate, R.A. (2001). Chemical synthesis and biological activity of rat INSL3. J. Pept. Sci. 7, 495–501.10.1002/psc.344Search in Google Scholar

Steiner, D.F. (1998). The proprotein convertases. Curr. Opin. Chem. Biol. 2, 31–39.10.1016/S1367-5931(98)80033-1Search in Google Scholar

von Heijne, G. (1986). A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 14, 4683–4690.10.1093/nar/14.11.4683Search in Google Scholar PubMed PubMed Central

Zimmermann, S., Steding, G., Emmen, J.M., Brinkmann, A.O., Nayernia, K., Holstein, A.F., Engel, W., and Adham, I.M. (1999). Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. Mol. Endocrinol. 13, 681–691.10.1210/mend.13.5.0272Search in Google Scholar PubMed