The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Insl3  -  insulin-like 3

Mus musculus

Synonyms: Insulin-like 3, Ley I-L, Ley-I-L, Leydig insulin-like peptide, Relaxin-like factor, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Insl3


High impact information on Insl3

  • Leydig insulin-like hormone (Insl3) is a member of the insulin hormone superfamily expressed in the developing testis [5].
  • Cryptorchidism in mice mutant for Insl3 [5].
  • Finally, a constitutively active form of Rlf can stimulate transcriptional activation and cell growth [6].
  • Stimulation of gene induction and cell growth by the Ras effector Rlf [6].
  • These results suggest that Insl3-mediated activity induces gubernaculum development and precludes a role of androgen in this process [7].

Chemical compound and disease context of Insl3


Biological context of Insl3

  • Transgenic overexpression of Insl3, the cognate ligand for Lgr8, does not rescue the mutant phenotype of Lgr7-deficient female mice indicating nonoverlapping functions of the two receptors [10].
  • Despite its importance for male sex differentiation and reproductive function in both sexes, very little is known regarding the molecular mechanisms that regulate Insl3 expression [11].
  • We show here that mice mutant for Insl3 are viable, but exhibit bilateral cryptorchidism due to developmental abnormalities of the gubernaculum, resulting in abnormal spermatogenesis and infertility [5].
  • RESULTS: Of the mice 11 Insl3 homozygote males had significantly impaired testicular descent at embryonic day 16.5 and birth (p <0.01), and the cord was thin and elongated, while 14 heterozygotes and 7 wild-types had normal testicular descent [12].
  • MATERIALS AND METHODS: Mice with Insl3 homozygotes (-/-), heterozygotes (+/-) and wild-types (+/+) were examined at embryonic day 16.5 and birth [12].

Anatomical context of Insl3


Associations of Insl3 with chemical compounds

  • Male sexual differentiation relies upon testicular secretion of the hormones testosterone, Mullerian inhibiting substance, and insulin-3 (Insl3) [3].
  • Tryptophan B27 in the relaxin-like factor (RLF) is crucial for RLF receptor-binding [15].
  • Consistent with this observation, alanine substitution of one of these residues (K687) in Rlf significantly reduced affinity for Ras-GTP [16].
  • Tissues were fixed in 10% neutral buffered formalin, and utilizing two different antibodies to relaxin-like factor, W3 rabbit anti-bovine and 2-8F mouse anti-bovine, relaxin-like factor was localized in fibroblast-like cells [17].
  • Gubernaculum cells in primary culture showed an increased uptake of 5-bromo-2'-deoxyuridine in the presence of RLF compared with controls [4].

Physical interactions of Insl3


Other interactions of Insl3


Analytical, diagnostic and therapeutic context of Insl3


  1. GREAT/LGR8 is the only receptor for insulin-like 3 peptide. Bogatcheva, N.V., Truong, A., Feng, S., Engel, W., Adham, I.M., Agoulnik, A.I. Mol. Endocrinol. (2003) [Pubmed]
  2. Over expression of insulin-like 3 does not prevent cryptorchidism in GNRHR or HOXA10 deficient mice. Feng, S., Bogatcheva, N.V., Truong, A., Engel, W., Adham, I.M., Agoulnik, A.I. J. Urol. (2006) [Pubmed]
  3. A molecular basis for estrogen-induced cryptorchidism. Nef, S., Shipman, T., Parada, L.F. Dev. Biol. (2000) [Pubmed]
  4. Relaxin-like factor (RLF) serum concentrations and gubernaculum RLF receptor display in relation to pre- and neonatal development of rats. Boockfor, F.R., Fullbright, G., Büllesbach, E.E., Schwabe, C. Reproduction (2001) [Pubmed]
  5. Cryptorchidism in mice mutant for Insl3. Nef, S., Parada, L.F. Nat. Genet. (1999) [Pubmed]
  6. Stimulation of gene induction and cell growth by the Ras effector Rlf. Wolthuis, R.M., de Ruiter, N.D., Cool, R.H., Bos, J.L. EMBO J. (1997) [Pubmed]
  7. The overexpression of the insl3 in female mice causes descent of the ovaries. Adham, I.M., Steding, G., Thamm, T., Büllesbach, E.E., Schwabe, C., Paprotta, I., Engel, W. Mol. Endocrinol. (2002) [Pubmed]
  8. Involvement of insulin-like factor 3 (Insl3) in diethylstilbestrol-induced cryptorchidism. Emmen, J.M., McLuskey, A., Adham, I.M., Engel, W., Verhoef-Post, M., Themmen, A.P., Grootegoed, J.A., Brinkmann, A.O. Endocrinology (2000) [Pubmed]
  9. Female mice carrying a ubiquitin promoter-Insl3 transgene have descended ovaries and inguinal hernias but normal fertility. Koskimies, P., Suvanto, M., Nokkala, E., Huhtaniemi, I.T., McLuskey, A., Themmen, A.P., Poutanen, M. Mol. Cell. Endocrinol. (2003) [Pubmed]
  10. Genetic targeting of relaxin and insulin-like factor 3 receptors in mice. Kamat, A.A., Feng, S., Bogatcheva, N.V., Truong, A., Bishop, C.E., Agoulnik, A.I. Endocrinology (2004) [Pubmed]
  11. The orphan nuclear receptor NR4A1 regulates insulin-like 3 gene transcription in Leydig cells. Robert, N.M., Martin, L.J., Tremblay, J.J. Biol. Reprod. (2006) [Pubmed]
  12. Leydig insulin-like hormone, gubernacular development and testicular descent. Kubota, Y., Nef, S., Farmer, P.J., Temelcos, C., Parada, L.F., Hutson, J.M. J. Urol. (2001) [Pubmed]
  13. Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. Zimmermann, S., Steding, G., Emmen, J.M., Brinkmann, A.O., Nayernia, K., Holstein, A.F., Engel, W., Adham, I.M. Mol. Endocrinol. (1999) [Pubmed]
  14. Increase in final stages of follicular atresia and premature decay of corpora lutea in Insl3-deficient mice. Spanel-Borowski, K., Schäfer, I., Zimmermann, S., Engel, W., Adham, I.M. Mol. Reprod. Dev. (2001) [Pubmed]
  15. Tryptophan B27 in the relaxin-like factor (RLF) is crucial for RLF receptor-binding. Büllesbach, E.E., Schwabe, C. Biochemistry (1999) [Pubmed]
  16. Characterization of the Ras binding domain of the RalGDS-related protein, RLF. O'gara, M.J., Zhang, X., Baker, L., Marshall, M.S. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  17. Immunohistochemical localization of relaxin-like factor/insulin-like peptide-3 in the bovine corpus luteum. Nichols, N., Binta, H., Fields, P.A., Drost, M., Chang, S.M., Ivell, R., Fields, M.J. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  18. Changes in the reproductive system of male mice immunized with a GnRH-analogue conjugated to mycobacterial hsp70. Hannesdóttir, S.G., Han, X., Lund, T., Singh, M., Van Der Zee, R., Roitt, I.M., Delves, P.J. Reproduction (2004) [Pubmed]
  19. Hormonal control of gubernaculum development during testis descent: gubernaculum outgrowth in vitro requires both insulin-like factor and androgen. Emmen, J.M., McLuskey, A., Adham, I.M., Engel, W., Grootegoed, J.A., Brinkmann, A.O. Endocrinology (2000) [Pubmed]
  20. Molecular cloning and expression of the relaxin-like factor from the mouse testis. Pusch, W., Balvers, M., Ivell, R. Endocrinology (1996) [Pubmed]
  21. The mouse relaxin-like factor gene and its promoter are located within the 3' region of the JAK3 genomic sequence. Koskimies, P., Spiess, A.N., Lahti, P., Huhtaniemi, I., Ivell, R. FEBS Lett. (1997) [Pubmed]
  22. Different insulin-like 3 (INSL3) gene mutations not associated with human cryptorchidism. Marin, P., Ferlin, A., Moro, E., Garolla, A., Foresta, C. J. Endocrinol. Invest. (2001) [Pubmed]
  23. The primary structure and the disulfide links of the bovine relaxin-like factor (RLF). Büllesbach, E.E., Schwabe, C. Biochemistry (2002) [Pubmed]
  24. Relaxin-like factor gene is highly expressed in the bovine ovary of the cycle and pregnancy: sequence and messenger ribonucleic acid analysis. Bathgate, R., Balvers, M., Hunt, N., Ivell, R. Biol. Reprod. (1996) [Pubmed]
WikiGenes - Universities