L'insulin-like 3 (Insl3) est une protéine qui, chez l'humain, est codée par le gène INSL3[5],[6].
La protéine codée par ce gène est une hormone de type insuline produite principalement dans les tissus gonadiques des mâles et des femelles. Des études sur modèle murin suggèrent l'implication de ce gène dans le développement du tractus urogénital(en) et de la fertilité féminine. L'INSL-3 initie la progression méiotique dans les ovocytes enfermés dans un follicule en médiant une réduction de la concentration intraovoculaire d'AMPc par l'activation du récepteur 8 couplé à la protéine G (LGR8)[7]. Elle peut également agir comme une hormone pour réguler la croissance et la différenciation du gubernaculum et ainsi médier la descente testiculaire intraabdominale. Les mutations de ce gène peuvent entraîner une cryptorchidie, mais n'en sont pas une cause fréquente[6].
↑Burkhardt E, Adham IM, Brosig B, Gastmann A, Mattei MG, Engel W, «Structural organization of the porcine and human genes coding for a Leydig cell-specific insulin-like peptide (LEY I-L) and chromosomal localization of the human gene (INSL3)», Genomics, vol.20, no1, , p.13–9 (PMID8020942, DOI10.1006/geno.1994.1121)
Lai KS, Jin Y, Graham DK, Witthuhn BA, Ihle JN, Liu ET, «A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells», The Journal of Biological Chemistry, vol.270, no42, , p.25028–36 (PMID7559633, DOI10.1074/jbc.270.42.25028)
Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnston JA, Candotti F, O'Shea JJ, «Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)», Nature, vol.377, no6544, , p.65–8 (PMID7659163, DOI10.1038/377065a0, Bibcode1995Natur.377...65M, S2CID4329874)
Tashima LS, Hieber AD, Greenwood FC, Bryant-Greenwood GD, «The human Leydig insulin-like (hLEY I-L) gene is expressed in the corpus luteum and trophoblast», The Journal of Clinical Endocrinology and Metabolism, vol.80, no2, , p.707–10 (PMID7852540, DOI10.1210/jc.80.2.707)
Witthuhn BA, Silvennoinen O, Miura O, Lai KS, Cwik C, Liu ET, Ihle JN, «Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells», Nature, vol.370, no6485, , p.153–7 (PMID8022486, DOI10.1038/370153a0, Bibcode1994Natur.370..153W, S2CID11711979)
Kawamura M, McVicar DW, Johnston JA, Blake TB, Chen YQ, Lal BK, Lloyd AR, Kelvin DJ, Staples JE, Ortaldo JR, «Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes», Proceedings of the National Academy of Sciences of the United States of America, vol.91, no14, , p.6374–8 (PMID8022790, PMCID44204, DOI10.1073/pnas.91.14.6374, Bibcode1994PNAS...91.6374K)
Burkhardt E, Adham IM, Hobohm U, Murphy D, Sander C, Engel W, «A human cDNA coding for the Leydig insulin-like peptide (Ley I-L)», Human Genetics, vol.94, no1, , p.91–4 (PMID8034302, DOI10.1007/BF02272850, S2CID11255499)
Adham IM, Burkhardt E, Benahmed M, Engel W, «Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells», The Journal of Biological Chemistry, vol.268, no35, , p.26668–72 (PMID8253799, DOI10.1016/S0021-9258(19)74364-6)
Verbsky JW, Bach EA, Fang YF, Yang L, Randolph DA, Fields LE, «Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells», The Journal of Biological Chemistry, vol.271, no24, , p.13976–80 (PMID8662778, DOI10.1074/jbc.271.24.13976)
Candotti F, Oakes SA, Johnston JA, Giliani S, Schumacher RF, Mella P, Fiorini M, Ugazio AG, Badolato R, Notarangelo LD, Bozzi F, Macchi P, Strina D, Vezzoni P, Blaese RM, O'Shea JJ, Villa A, «Structural and functional basis for JAK3-deficient severe combined immunodeficiency», Blood, vol.90, no10, , p.3996–4003 (PMID9354668, DOI10.1182/blood.V90.10.3996)
Bozzi F, Lefranc G, Villa A, Badolato R, Schumacher RF, Khalil G, Loiselet J, Bresciani S, O'Shea JJ, Vezzoni P, Notarangelo LD, Candotti F, «Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment», British Journal of Haematology, vol.102, no5, , p.1363–6 (PMID9753072, DOI10.1111/j.1365-2141.1998.tb08990.x, S2CID31606560)
Krausz C, Quintana-Murci L, Fellous M, Siffroi JP, McElreavey K, «Absence of mutations involving the INSL3 gene in human idiopathic cryptorchidism», Molecular Human Reproduction, vol.6, no4, , p.298–302 (PMID10729310, DOI10.1093/molehr/6.4.298)
Koskimies P, Virtanen H, Lindström M, Kaleva M, Poutanen M, Huhtaniemi I, Toppari J, «A common polymorphism in the human relaxin-like factor (RLF) gene: no relationship with cryptorchidism», Pediatric Research, vol.47, no4 Pt 1, , p.538–41 (PMID10759163, DOI10.1203/00006450-200004000-00020)
Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K, «STAM2, a new member of the STAM family, binding to the Janus kinases», FEBS Letters, vol.477, nos1–2, , p.55–61 (PMID10899310, DOI10.1016/S0014-5793(00)01760-9, S2CID31811757)
Schumacher RF, Mella P, Badolato R, Fiorini M, Savoldi G, Giliani S, Villa A, Candotti F, Tampalini A, O'Shea JJ, Notarangelo LD, «Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism», Human Genetics, vol.106, no1, , p.73–9 (PMID10982185, DOI10.1007/s004390051012)
Tomboc M, Lee PA, Mitwally MF, Schneck FX, Bellinger M, Witchel SF, «Insulin-like 3/relaxin-like factor gene mutations are associated with cryptorchidism», The Journal of Clinical Endocrinology and Metabolism, vol.85, no11, , p.4013–8 (PMID11095425, DOI10.1210/jc.85.11.4013)
Lim HN, Raipert-de Meyts E, Skakkebaek NE, Hawkins JR, Hughes IA, «Genetic analysis of the INSL3 gene in patients with maldescent of the testis», European Journal of Endocrinology, vol.144, no2, , p.129–37 (PMID11182749, DOI10.1530/eje.0.1440129)
