Alternative titles; symbols
HGNC Approved Gene Symbol: INSL4
Cytogenetic location: 9p24.1 Genomic coordinates (GRCh38): 9:5,231,419-5,235,304 (from NCBI)
Insulin (176730) and insulin-like growth factors, such as INSL4, belong to a family of polypeptides essential for proper regulation of physiologic processes such as energy metabolism, cell proliferation, development, and differentiation (summary by Koman et al., 1996).
Chassin et al. (1995) identified a novel member of the insulin gene superfamily by screening a cDNA library subtracted for first-trimester-expressed genes of the placenta. The gene, which the authors designated 'early placenta insulin-like peptide' (EPIL), encodes a putative 139-amino acid protein with structural similarities to insulin and other related sequences. RT-PCR showed expression in the placenta and uterus.
Seeking novel secreted molecules involved in cell growth control, Koman et al. (1996) also cloned a cDNA encoding INSL4, which they named placentin, from a human cDNA library enriched in sequences from cytotrophoblast cells of first trimester placenta. Placentin is composed of 2 peptide chains of apparent molecular masses of 4 and 13 kD.
The INSL4 gene contains 2 exons, as does insulin and relaxin (see 179730). Its single intron is about 2 kb long (Chassin et al., 1995).
By in situ hybridization, Chassin et al. (1995) mapped the INSL4 gene to chromosome 9p24.
By PCR analysis of YACs covering the distal part of 9p and by use of a human-rodent radiation hybrid panel, Veitia et al. (1998) mapped the INSL4 gene to 9p24.1-p23.3 and eliminated it as a candidate for the 9p- syndrome.
Koman et al. (1996) found that recombinant expression of placentin cDNA resulted in effects closely mimicking those of insulin, but the effects were not mediated by the insulin receptor, as shown by the lack of tyrosine phosphorylation of this receptor upon placentin treatment. Moreover, production of chorionic gonadotropin (see 118850), a marker of trophoblast differentiation, was increased by treatment with placentin but was unaffected by insulin. The results suggested that placentin may participate in the cellular proliferation and/or differentiation processes during placental development.
Mock et al. (1999) reported the usefulness of a specific immunoassay, based on 2 monoclonal antipeptide antibodies, for the detection of pro-EPIL forms in biologic fluids during pregnancy. Pro-EPIL molecular forms were detected in both amniotic fluid and maternal serum of pregnant women. At 12 to 16 weeks of pregnancy, the pro-EPIL level was higher in amniotic fluid than in maternal serum. As gestation advanced, the concentration of pro-EPIL forms decreased in amniotic fluid, while its level increased in maternal serum. Interestingly, in amniotic fluid, the pattern of pro-EPIL concentration during pregnancy was very similar to that observed for human chorionic gonadotropin (CG) and its free subunits. The pattern of serum pro-EPIL concentration was similar to that of the free alpha subunit. The authors concluded that together with their previous immunohistochemical observations, these results indicated that pro-EPIL is preferentially secreted by cytotrophoblasts in amniotic fluid and that the biosynthesis of CG subunits and EPIL may be regulated by common pathways. Furthermore, the results suggested that EPIL may play a critical physiologic role during embryonic and fetal development.
Mock et al. (2000) studied the expression of pro-EPIL peptides in chromosomally abnormal pregnancies, namely trisomy 21 (see 190685) and 18. They measured EPIL peptide levels in amniotic fluid and maternal serum from 16 pregnancies with trisomy 21 and 14 with trisomy 18 and compared them to levels detected in amniotic fluid and maternal serum from 33 chromosomally normal pregnancies between 12 and 32 weeks of gestation. Pro-EPIL peptide levels were significantly higher in amniotic fluids from trisomy 21 pregnancies than in amniotic fluid from chromosomally normal pregnancies, whereas there was only a trend towards an increase in pro-EPIL peptide levels in maternal serum. In a limited matched gestational age range (15 to 17 weeks), it was confirmed that pro-EPIL peptide levels were significantly higher in amniotic fluid from trisomy 21 pregnancies than in amniotic fluid from normal pregnancies.
Chassin, D., Laurent, A., Janneau, J.-L., Berger, R., Bellet, D. Cloning of a new member of the insulin gene superfamily (INSL4) expressed in human placenta. Genomics 29: 465-470, 1995. [PubMed: 8666396] [Full Text: https://doi.org/10.1006/geno.1995.9980]
Koman, A., Cazaubon, S., Couraud, P.-O., Ullrich, A., Strosberg, A. D. Molecular characterization and in vitro biological activity of placentin, a new member of the insulin gene family. J. Biol. Chem. 271: 20238-20241, 1996. [PubMed: 8702754] [Full Text: https://doi.org/10.1074/jbc.271.34.20238]
Mock, P., Frydman, R., Bellet, D., Chassin, D., Bischof, P., Campana, A., Bidart, J. M. Expression of pro-EPIL peptides encoded by the insulin-like 4 (INSL4) gene in chromosomally abnormal pregnancies. J. Clin. Endocr. Metab. 85: 3941-3944, 2000. [PubMed: 11061561] [Full Text: https://doi.org/10.1210/jcem.85.10.6925]
Mock, P., Frydman, R., Bellet, D., Diawara, D. A., Lavaissiere, L., Troalen, F., Bidart, J.-M. Pro-EPIL forms are present in amniotic fluid and maternal serum during normal pregnancy. J. Clin. Endocr. Metab. 84: 2253-2256, 1999. [PubMed: 10372742] [Full Text: https://doi.org/10.1210/jcem.84.6.5888]
Veitia, R., Laurent, A., Quintana-Murci, L., Ottolenghi, C., Fellous, M., Vidaud, M., McElreavey, K. The INSL4 gene maps close to WI-5527 at 9p24.1-p23.3 clustered with two relaxin genes and outside the critical region for the monosomy 9p syndrome. Cytogenet. Cell Genet. 81: 275-277, 1998. [PubMed: 9730618] [Full Text: https://doi.org/10.1159/000015045]