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Gene Review

Insl3  -  insulin-like 3

Rattus norvegicus

Synonyms: Insulin-like 3, Ley-I-L, Leydig insulin-like peptide, Relaxin-like factor, Rlf
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Disease relevance of Insl3

  • We generated (by genetic immunization) and validated a novel antirat Insl3 antibody, which we used to characterize immunoexpression of Insl3 in rat Leydig cells (LCs) from fetal life until adulthood and its relationship to cryptorchidism [1].

High impact information on Insl3

  • We found that LH stimulates Leydig insulin-like 3 (INSL3) transcripts in ovarian theca and testicular Leydig cells [2].
  • Ral-specific guanine-nucleotide exchange factors such as RalGDS, Rlf and RGL interact with activated Ras and cooperate with Ras in the transformation of murine fibroblasts [2-5] [3].
  • DBP treatment suppressed expression of both P450 side-chain cleavage enzyme and Insl3 at E19.5, but flutamide exposure had no effect on either protein, demonstrating that Insl3 expression in fetal rat LCs is not androgen regulated [1].
  • The expression of the RLF/INSL3 gene is reduced in Leydig cells of the aging rat testis [4].
  • In order to test whether this is a property of the HPG axis, or of the Leydig cells themselves, RLF/INSL3 was used as an independent marker to assess rat Leydig cell differentiation status [4].

Associations of Insl3 with chemical compounds

  • Additionally, we observed reduced mRNA expression of the nuclear receptor SF-1, which regulates certain steps in steroid synthesis, and reduced expression of the cryptorchidism-associated Insl-3 [5].

Other interactions of Insl3


  1. 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. McKinnell, C., Sharpe, R.M., Mahood, K., Hallmark, N., Scott, H., Ivell, R., Staub, C., Jégou, B., Haag, F., Koch-Nolte, F., Hartung, S. Endocrinology (2005) [Pubmed]
  2. Paracrine regulation of mammalian oocyte maturation and male germ cell survival. Kawamura, K., Kumagai, J., Sudo, S., Chun, S.Y., Pisarska, M., Morita, H., Toppari, J., Fu, P., Wade, J.D., Bathgate, R.A., Hsueh, A.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. Ras-independent activation of Ral by a Ca(2+)-dependent pathway. Hofer, F., Berdeaux, R., Martin, G.S. Curr. Biol. (1998) [Pubmed]
  4. The expression of the RLF/INSL3 gene is reduced in Leydig cells of the aging rat testis. Paust, H.J., Wessels, J., Ivell, R., Mukhopadhyay, A.K. Exp. Gerontol. (2002) [Pubmed]
  5. Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis. Borch, J., Metzdorff, S.B., Vinggaard, A.M., Brokken, L., Dalgaard, M. Toxicology (2006) [Pubmed]
  6. Solid-phase synthesis of ovine Leydig cell insulin-like peptide--a putative ovine relaxin? Dawson, N.F., Tan, Y.Y., Macris, M., Otvos, L., Summers, R.J., Tregear, G.W., Wade, J.D. J. Pept. Res. (1999) [Pubmed]
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