Inhibition of iodine-125-labeled human follitropin binding to testicular receptor by epidermal growth factor and synthetic peptides - PubMed

Inhibition of iodine-125-labeled human follitropin binding to testicular receptor by epidermal growth factor and synthetic peptides

P M Sluss et al. Biochemistry. 1986.

Abstract

Two tetrapeptide sequence homologies between mouse epidermal growth factor precursor (mEGFP) and human follitropin (FSH) were revealed by a computer program that identifies identical residues among polypeptide sequences. The two tetrapeptides, Lys-Thr-Cys-Thr (KTCT) and Thr-Arg-Asp-Leu (TRDL), are present in the hormone-specific beta subunit of FSH from all species studied. These tetrapeptides are not present in the alpha subunit, which is common to all pituitary glycoprotein hormones. Both tetrapeptides are also found in mEGFP, and one tetrapeptide, TRDL, is located within the 53-residue form of mEGF purified from mouse submaxillary glands. Computer-generated hydropathy profiles predicted that both tetrapeptides are located in hydrophilic portions of the FSH beta subunit and that TRDL is in a hydrophilic portion of commercially available mEGF. Therefore, the tetrapeptides might be accessible to receptor binding sites for FSH. We report that mEGF inhibits binding of 125I-labeled human FSH to receptors in testis by 50% (I50) at a concentration of 1.8 X 10(-5) M. No binding inhibition was observed by GnRH or arginine-vasopressin at 10(-4) M, neither of which contain the tetrapeptide sequences. FSH beta subunit, which contains both tetrapeptides, also inhibited binding (I50 = 9 X 10(-8) M) of 125I-labeled human FSH to testis receptor. Thus, it appears that FSH beta subunit and mEGF are capable of inhibiting binding of FSH to testicular FSH receptors, presumably through interactions that include the homologous tetrapeptides. This presumption was supported by the observation that the synthetic tetrapeptides (KTCT or TRDL) were also active in inhibiting binding of 125I-labeled human FSH to testis receptor.

Similar articles

• Identification of a receptor binding region on the beta subunit of human follicle-stimulating hormone.

  Schneyer AL, Sluss PM, Huston JS, Ridge RJ, Reichert LE Jr. Schneyer AL, et al. Biochemistry. 1988 Jan 26;27(2):666-71. doi: 10.1021/bi00402a026. Biochemistry. 1988. PMID: 3126813

• A synthetic peptide corresponding to human FSH beta-subunit 33-53 binds to FSH receptor, stimulates basal estradiol biosynthesis, and is a partial antagonist of FSH.

  Santa Coloma TA, Dattatreyamurty B, Reichert LE Jr. Santa Coloma TA, et al. Biochemistry. 1990 Feb 6;29(5):1194-200. doi: 10.1021/bi00457a015. Biochemistry. 1990. PMID: 2108722

• Biochemical properties of the testicular follitropin-receptor system.

  Reichert LE Jr, Dias JA, Fletcher PW, O'Neill WC. Reichert LE Jr, et al. Ann N Y Acad Sci. 1982;383:135-50. doi: 10.1111/j.1749-6632.1982.tb23166.x. Ann N Y Acad Sci. 1982. PMID: 6283987 Review.

Cited by

• A receptor-binding region in human choriogonadotropin/lutropin beta subunit.

  Keutmann HT, Charlesworth MC, Mason KA, Ostrea T, Johnson L, Ryan RJ. Keutmann HT, et al. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2038-42. doi: 10.1073/pnas.84.7.2038. Proc Natl Acad Sci U S A. 1987. PMID: 3470775 Free PMC article.

• Conversion of human choriogonadotropin into a follitropin by protein engineering.

  Campbell RK, Dean-Emig DM, Moyle WR. Campbell RK, et al. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):760-4. doi: 10.1073/pnas.88.3.760. Proc Natl Acad Sci U S A. 1991. PMID: 1899483 Free PMC article.

• Synthetic peptides based upon a three-dimensional model for the receptor recognition site of follicle-stimulating hormone exhibit antagonistic or agonistic activity at low concentrations.

  Hage-van Noort M, Puijk WC, Plasman HH, Kuperus D, Schaaper WM, Beekman NJ, Grootegoed JA, Meloen RH. Hage-van Noort M, et al. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3922-6. doi: 10.1073/pnas.89.9.3922. Proc Natl Acad Sci U S A. 1992. PMID: 1315043 Free PMC article.

• Allosteric modulators of glycoprotein hormone receptors: discovery and therapeutic potential.

  Arey BJ. Arey BJ. Endocrine. 2008 Aug-Dec;34(1-3):1-10. doi: 10.1007/s12020-008-9098-2. Epub 2008 Oct 28. Endocrine. 2008. PMID: 18956257 Review.

Publication types

MeSH terms

Substances