Abstract
A procedure is described for isolation from human pituitary glands of a peptide with the amino acid sequence of the first 43 residues of human growth hormone, hGH (1–43). The peptide was recovered in a yield of 12 mg per 1000 pituitary glands. In a radioimmunoassay for hGH the peptide was unreactive when tested at 1 µg/ml and therefore if it does circulate, it probably has gone underected in blood. Growth-promoting activity as measured by the tibial line procedure was low but detectable; however, the log dose response was not parallel to that of hGH. Separate studies indicated the hGH (1–43) was a potent potentiator of insulin action suggesting physiologic significance. Further, because the peptide can be a cleavage product of the major form of hGH but not of its 20,000-dalton variant, importance is indicated for the multiple forms of the hormone.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ambler, R. P. (1972). Carboxypeptidase A and B.Methods Enzymol. 25, 262–272.
Anon (1971).In Sequence (Beckman, Instruments, Palo Alto, CA)1971(March), 31–37.
Anon (1975).In Sequence (Beckman Instruments, Palo Alto, CA)1975(April), No. 7.
Armstrong, J. McD., Bornstein, J., Bromley, J. O., Macaulay, S. L., and Ng, F. M. (1983). Parallel insulin-like actions of human growth hormone and its part sequence hGH7-13.Acta Endocrinol. 102, 492–498.
Chang, J. Y., Brauer, D., and Wittmann-Liebold, B. (1978). Micro-sequence analysis of peptides and proteins using 4,N,N-dimethylaminoazobenzene 4′isothiocynate/phenylthiocyanate double coupling method.FEBS Lett. 93, 205–214.
Davis, B. J. (1964). Disc electrophoresis. II. Method and application to human serum proteins.Ann. N. Y. Acad. Sci. 121, 404–427.
DeNoto, F. M., Moore, D. D., and Goodman, H. M. (1981). Human growth hormone DNA sequence and mRNA structure: Possible alternative splicing.Nucleic Acid Res. 9, 3719–3730.
Dryburgh, J. R., Rudman, C. G., and Stebbing, N. (1983). The effect of a fragment of human growth hormone on induced hyperglycemia in normal and glucose intolerant animals.Endocrinology 112, (Suppl.), 379 (abstr.).
Frigeri, L. G., and Ling, N. (1982). Biological activities of the synthetic fragment 32–46 of the human growth hormone sequence.Endocrinology 110 (Suppl.), 101 (abstr.).
Frigeri, L. G., Peterson, S. M., and Lewis, U. J. (1979). The 20,000 dalton structural variant of human growth hormone: Lack of some early insulin-like effects.Biochem. Biophys. Res. Commun. 91, 778–782.
Frigeri, L. G., Ling, N., Robel, G., VanderLaan, W. P., and Lewis, U. J., (1984). Amino-terminal peptides of growth hormone increasein vivo glucose utilization in obese mice, submitted.
Goodman, H. M., DeNoto, F., Fiddes, J. C., Hallewell, R. A., Page, G. S., Smith, S., and Tischer, E. (1980). Structure and evolution of growth hormone related genes. In Scott, W. A., Werner, R., Joseph, D. R., and Schultz, J., (eds.),Miami Winter Symposium, Vol. 17, Academic, New York, pp. 155–178.
Gordon, D. F., Quick, D. P., Erwin, C. R., Donelson, J. E., and Maurer, R. A. (1983). Nucleotide sequence of the bovine growth hormone chromosomal gene.Mol. Cell. Endocrinol. 33, 81–95.
Greenspan, F. S., Li, C. H., Simpson, M. C., and Evans, H. M. (1949). Bioassay of hypophyseal growth hormone: The tibia test.Endocrinology 45, 455–463.
Guyer, R. L., and Todd, C. W. (1975). Protein sequencing: Thermal conversion of thiazolinone derivatives of amino acids to thiohydantoins.Anal. Biochem. 66, 400–404.
Hearn, M. T. W., Grego, B., and Chapman, G. E. (1983). Separation and assignment of the tryptic peptides of human growth hormone (hGH) and the 20K dalton hGH variant by reversed phase high performance liquid chromatography.J. Liq. Chromatogr. 6, 216–220.
Kohr, W. J., Keck, R., and Harkins, R. N. (1982). Characterization of intact and trypsin-digested biosynthetic human growth hormone by high-pressure liquid chromatography.Anal. Biochem. 122, 348–359.
Lewis, U. J. (1984). Variants of growth hormone and prolactin and their posttranslational modifications.Annu. Rev. Physiol. 46, 33–42.
Lewis, U. J., Singh, R. N. P., Lindsey, T. T., Seavey, B. K., and Lambert, T. H. (1974). Enzymically modified growth hormones and the diabetogenic activity of human growth hormone. In Raiti, S. (ed.),Advances in Human Growth Hormone Research, DHEW Publication No. 74-612, U.S. Government Printing Office, Washington, D. C., pp. 349–363.
Lewis, U. J., Dunn, J. T., Bonewald, L. F., Seavey, B. K., and VanderLaan, W. P. (1978). A naturally occurring structural variant of human growth hormone.J. Biol. Chem. 253, 2679–2687.
Lewis, U. J., Singh, R. N. P., Bonewald, L. F., Lewis, L. J., and VanderLaan, W. P. (1979). Human growth hormone: Additional members of the complex.Endocrinology 104, 1256–1265.
Lewis, U. J., Bonewald, L. F., and Lewis, L. J. (1980). The 20,000 dalton variant of human growth hormone: Location of the amino acid deletion.Biochem. Biophys. Res. Commun. 92, 511–516.
Lewis, U. J., Singh, R. N. P., Bonewald, L. F., and Seavey, B. K. (1981). Altered proteolytic cleavage of human growth hormone as a result of deamidation.J. Biol. Chem. 256, 11645–11650.
Li, C. H., Dixon, J. S., Gordon, D., and Knorr, J. (1972). Amino acid sequence of sheep pituitary growth hormone.Int. J. Peptide Protein Res. 4, 151–153.
Ng. F. M., and Bornstein, J. (1979). Insulin-potentiating action of a synthetic amino terminal fragment of human growth hormone (hGH 1–15) in streptozotocin diabetic mice.Diabetes 28, 1126–1130.
Robinson, A. B., and Rudd, C. J. (1974). Deamidation of glutaminyl and asparaginyl residues in peptides and proteins.Curr. Top. Cell. Regul. 8, 247–295.
Seeburg, P. H., Shine, J., Martial, J. A., Baxter, J. D., and Goodman, H. M. (1977). Nucleotide sequence and amplification in bacteria of structural gene for rat growth hormone.Nature 270, 486–494.
Singh, R. N. P., and Lewis, U. J. (1981). Procedure for isolation of the 20,000 dalton variant of human growth hormone.Prep. Biochem. 11, 559–570.
Smithies, O., Gibson, D., Fanning, E. M., Goodfleish, R. M., Gilman, J. G., and Ballantyne, D. L. (1971). Quantitative procedures for use with the Edman-Begg sequenator. Partial sequences of two unusual immunoglobulin light chains, Rzf and Sac.Biochemistry 10, 4912–4921.
Wallis, M. (1973). The primary structure of bovine growth hormone.FEBS Lett. 35, 11–14.
Wallis, M. (1980). Growth hormone: Deletions in the protein and introns in the gene.Nature 284, 512.
Weber, K., and Osborn, M. (1969). The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide electrophoresis.J. Biol. Chem. 244, 4406–4412.
Yudaev, N. A., Pankov, Yu. A., Keda, Yu. M., Sazina, E. T., Osipova, T. A., Shwachkin, Yu. P., and Ryabtsev, M. N. (1983). The effect of synthetic fragment 31–44 of human growth hormone on glucose uptake by isolated adipose tissue.Biochem. Biophys. Res. Commun. 110, 866–872.
Zakin, M. M., Poskus, E., Dellacha, J. M., Paladini, A. C., and Santome, J. A. (1973). The amino acid sequence of equine growth hormone.FEBS Lett. 34, 353–355.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Singh, R.N.P., Seavey, B.K., Lewis, L.J. et al. Human growth hormone peptide 1–43: Isolation from pituitary glands. J Protein Chem 2, 425–436 (1983). https://doi.org/10.1007/BF01025416
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01025416