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Stability and Characterization of Human Growth Hormone

  • Chapter
Stability and Characterization of Protein and Peptide Drugs

Part of the book series: Pharmaceutical Biotechnology ((PBIO,volume 5))

Abstract

Human growth hormone (hGH) is a protein responsible for a wide range of growth-promoting effects in the body, either by direct action on receptors in various tissues or via stimulation of the release of other growth factors (Wilhelmi, 1982). Under hypothalamic control, the hormone is secreted from anterior pituitary granules, into the bloodstream in a pulsatile fashion (Evans et al., 1987). The average human pituitary weighs about 1 g, and is estimated to contain from 5 to 10 mg hGH (Daughaday, 1985). This chapter describes the history and clinical uses of the hormone, methods used for its characterization and analysis, and includes a discussion of hGH degradation reactions and its stability profile as well as a description of various hGH formulations.

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References

  • Abdel-Meguid, S. S., Shieh, H. S., Smith, W. W., Dayringer, H. E., Violand, B. N., and Bentle, L. A., 1987, Three dimensional structure of a genetically engineered variant of porcine growth hormone, Proc. Natl. Acad. Sci. USA 84:6434.

    Article  PubMed  CAS  Google Scholar 

  • Aloj, S., and Edelhoch, H., 1972, The molecular properties of human growth hormone, J. Biol Chem. 247:1146.

    PubMed  CAS  Google Scholar 

  • Aswad, D., 1984, Stoichiometric methylation of porcine adrenocorticotropin by protein carboxy methyltransferase requires deamidation of asparagine 25, J. Biol. Chem. 259:10714.

    PubMed  CAS  Google Scholar 

  • Aubert, M. L., Bewley, T. A., Grumbach, M. M., Kaplan, S. L., and Li, C. H., 1986, Structure-function studies on human growth hormone. Evidence that tertiary structure is essential for biological activity, Int. J. Pept. Protein Res. 28:45.

    Article  PubMed  CAS  Google Scholar 

  • Basuyaux, B., Paolucci, F., Clavies, C., Hervaud, E., Pau, B., and Peyrouset, A., 1987, Production and characterization of monoclonal antibodies to human growth hormone, Hybridoma 6:423.

    Article  PubMed  CAS  Google Scholar 

  • Beck, J. C., McGarry, E. E., Dryenfurth, I., and Venning, E. H., 1957, Metabolic effects of human and monkey growth hormone in man, Science 125:884.

    Article  PubMed  CAS  Google Scholar 

  • Becker, G. W., Bowsher, R. R., Mackellar, W. C., Poor, M. L., Tackitt, P. M., and Riggin, R. M., 1987, Chemical, physical, and biological characterization of a dimeric form of biosynthetic human growth hormone, Biotechnol Appl Bio-chem. 9:478.

    Article  CAS  Google Scholar 

  • Becker, G. W., Tackitt, P. M., Bromer, W. W., Lefeber, D. S., and Riggin, R. M., 1988, Isolation and characterization of a sulfoxide and a desamido derivative of biosynthetic human growth hormone, Biotechnol Appl. Biochem. 10:326.

    PubMed  CAS  Google Scholar 

  • Bennett, L. L., Weinberger, H., Escamilla, R., Margen, S., Li, C. H., and Evans, H. M., 1950, Failure of hypophyseal growth hormone to produce nitrogen storage in a girl with hypophyseal dwarfism, J. Clin. Endocrinol. 10:492.

    Article  CAS  Google Scholar 

  • Bewley, T. A., 1977, Optical activity of disulfide bonds in proteins. 1. Studies on plasmin modified human somatotropin, Biochemistry 16:209.

    Article  PubMed  CAS  Google Scholar 

  • Bewley, T. A., 1979, Circular dichroism of pituitary hormones, Recent Prog. Horm. Res. 35:155.

    PubMed  CAS  Google Scholar 

  • Bewley, T. A., and Li, C. H., 1970, Human pituitary growth hormone. XXII. The reduction and reoxidation of the hormone, Arch. Biochem. Biophys. 138:338.

    Article  PubMed  CAS  Google Scholar 

  • Bewley, T. A., and Li, C. H., 1972, Circular dichroism studies on human pituitary growth hormone and ovine pituitary lactogenic hormone, Biochemistry 11:884.

    Article  PubMed  CAS  Google Scholar 

  • Bewley, T. A., and Li, C. H., 1975, The chemistry of human pituitary growth hormone, Adv. Enzymol. 42:73.

    PubMed  CAS  Google Scholar 

  • Bewley, T. A., and Li, C. H., 1984, Conformational comparison of human pituitary growth hormone and human chorionic somatomammotropin (human placental lactogen) by second-order absorption spectroscopy, Arch. Biochem. Biophys. 233:219.

    Article  PubMed  CAS  Google Scholar 

  • Bewley, T. A., and Li, C. H., 1986, The conformation of monkey pituitary somatotropin, Arch. Biochem. Biophys. 248:646.

    Article  PubMed  CAS  Google Scholar 

  • Bewley, T. A., Brovetto-Cruz, J., and Li, C. H., 1969, Human pituitary growth hormone. Physicochemical investigations of the native and reduced-alkylated protein, Biochemistry 8:4701.

    Article  PubMed  CAS  Google Scholar 

  • Bornstein, P., and Balian, G., 1977, Cleavage at asn-gly bonds with hydroxylamine, Methods Enzymol. 47:132.

    Article  PubMed  CAS  Google Scholar 

  • Brems, D. N., Brown, P. L., and Becker, G. W., 1990, Equilibrium denaturation of human growth hormone and its cysteine-modified forms, J. Biol. Chem. 265:5504.

    PubMed  CAS  Google Scholar 

  • Bristow, A. F., and Jeffcoate, S. L., 1992, Analysis of therapeutic growth hormone preparations: Report of an interlaboratory collaborative study on growth hormone assay methodologies, Biologicals 20:221.

    Article  PubMed  CAS  Google Scholar 

  • Brown, P., Gajdusek, C. C., Gibbs, C. J., and Asher, D. M., 1985, Potential epidemic of Creutzfeldt-Jakob disease from human growth hormone therapy, N. Engl. J. Med. 313:728.

    Article  PubMed  CAS  Google Scholar 

  • Canova-Davis, E., Chloupek, R. C., Baldonado, I. P., Battersby, J. E., Spellman, M. W., Basa, L. J., O’Connor, B. H., Pearlman, R., Quan, C., Chakel, J. A., Stults, J. T., and Hancock, W. S., 1988, Analysis by FAB-MS and LC of proteins produced by either biosynthetic or chemical techniques, Am. Biotechnol. Lab. 6:8.

    CAS  Google Scholar 

  • Canova-Davis, E., Baldonado, I. P., Moore, J. A., Rudman, C. G., Bennet, W. F., and Hancock, W. S., 1990, Properties of a cleaved two-chain form of recombinant human growth hormone, Int. J. Pep. Protein Res. 35:17.

    Article  CAS  Google Scholar 

  • Cecil, R., 1963, Intramolecular bonds in proteins. I. The role of sulfur in proteins, in: The Proteins, 2nd ed., Vol. I (H. Neurath, ed.), Academic Press, New York, pp. 379–476.

    Google Scholar 

  • Cohen, F. E., and Kuntz, I. D., 1987, Prediction of the three-dimensional structure of human growth hormone, Proteins 2:162.

    Article  PubMed  CAS  Google Scholar 

  • Cunningham, B. C., and Wells, J. A., 1989, High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis, Science 244:1081.

    Article  PubMed  CAS  Google Scholar 

  • Cunningham, B. C., Mulkerrin, M. G., and Wells, J. A., 1991, Dimerization of human growth hormone by zinc, Science 253:545.

    Article  PubMed  CAS  Google Scholar 

  • Daughaday, W. F., 1985, The anterior pituitary, in: Williams’ Textbook of Endocrinology, 7th ed. (J. Wilson and D. W. Foster, eds.), Saunders, Philadelphia, pp. 568–613.

    Google Scholar 

  • Eckhardt, B. E., Oeswein, J. Q., and Bewley, T. A., 1991, Effect of freezing on aggregation of human growth hormone, Pharm. Res. 8:1360.

    Article  PubMed  CAS  Google Scholar 

  • Evans, H. M., and Long, J. A., 1921, The effect of the anterior lobe administered intraperitoneally upon growth, maturity, and oestrous cycles of the rat, Anat. Rec. 21:62.

    Google Scholar 

  • Evans, W. S., Faria, A. C., Christiansen, E., Ho, K. Y., Weiss, J., Rogol, A. D., Johnson, M. L., Blizzard, R. M. Veldhuis, J. D., and Thorner, M. O., 1987, Impact of intensive venous sampling on characterization of pulsatile GH release, Am. J. Physiol 252:549.

    Google Scholar 

  • Garcia-Rubino, L. H., 1989, Characterization of proteins during aggregation using turbidimetry, Chem. Eng. Commun. 80:193.

    Article  Google Scholar 

  • Garnick, R. L., Ross, M. J., and Dumee, C. P., 1988, Analysis of recombinant biologi-cals, in: Encyclopedia of Pharmaceutical Technology, Vol. 1 (J. Swarbrick and J. C. Boylan, eds.), Dekker, New York, pp. 253–313.

    Google Scholar 

  • Goeddel, D. V., Heyneker, H. L., Hozumi, T., Arentzen, R., Hakura, K., Yansura, D. G., Ross, M. J., Miozzari, G., Crea, R., and Seeburg, P. M., 1979, Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone, Nature 281:544.

    Article  PubMed  CAS  Google Scholar 

  • Graf, L., Li, C. H., Cheng, C. H. K., and Jibson, M. D., 1981, Two contiguous thrombin fragments of human somatotropin form a functionally active recombinant, but the two homologous fragments from sheep hormone do not, Biochemistry 20:7251.

    Article  PubMed  CAS  Google Scholar 

  • Graf, L., Li, C. H., and Jibson, M. D., 1982, Human somatotropin; selective removal with trypsin of residues 135–145 from the hormone molecule with no loss of biological activity, J. Biol. Chem. 257:2365.

    PubMed  CAS  Google Scholar 

  • Groesbeck, M. D., and Parlow, A. F., 1987, Highly improved precision of the hypoph-ysectomized female rat body weight gain bioassay for growth hormone by increased frequency of injections, avoidance of antibody formation, and other simple modifications, Endocrinology 120:2582.

    Article  PubMed  CAS  Google Scholar 

  • Hagenlocher, M., and Pearlman, R., 1989, Use of a substituted cyclodextrin for stabilization of human growth hormone, Pharm. Res. Suppl. 6:S30.

    Google Scholar 

  • Hancock, W. S., (ed.) 1984, Handbook of HPLC for the Separation of Amino Acids, Peptides and Proteins, CRC Press, Boca Raton, Fla.

    Google Scholar 

  • Hancock, W. S., 1986, Significance of purity in the manufacture of recombinant-DNA-derived proteins, Chromatogr. Forum 1:57.

    Google Scholar 

  • Hancock, W. S., Canova-Davis, E., Chloupek, R. C., Wu, S. L., Baldonado, I. P., Battersby, J. E., Spellman, M. W., Basa, L. J., and Chakel, J. A., 1988, The characterization of degradation products of recombinant human growth hormone, in: Therapeutic Peptides and Proteins: Assessing the New Technologies (D. Marshak and D. Liu, eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., pp. 95–118.

    Google Scholar 

  • Hashida, S., Ishikawa, E., Kato, Y., Imura, H., Mohri, Z., and Murakami, Y., 1987, Human growth hormone (hGH) in urine and its correlation to serum hGH examined by a highly sensitive sandwich enzyme immunoassay, Clin. Chim. Acta 162:229.

    Article  PubMed  CAS  Google Scholar 

  • Hindmarsh, P. C., and Brook, C. G., 1987, Effect of growth hormone on short normal children, Br. Med. J. Clin. Res. 295:573.

    Article  CAS  Google Scholar 

  • Hintz, R. L., Rosenfeld, R. G., Wilson, D. M., Bennett, A., Fenno, J., McClellan, B., and Swift, R., 1982, Biosynthetic methionyl-human growth hormone is biologically active in adult humans, Lancet 1:1276.

    Article  PubMed  CAS  Google Scholar 

  • Holladay, L. A., Hammonds, R. G., and Puett, D., 1974, Growth hormone conformation and conformational equilibria, Biochemistry 13:1653.

    Article  PubMed  CAS  Google Scholar 

  • Holmstrom, B., and Fholenhag, K., 1975, Characterization of human growth hormone preparations for the treatment of pituitary dwarfism: A comparison of concurrently used batches, J. Clin. Endocrinol. Metab. 40:856.

    Article  PubMed  CAS  Google Scholar 

  • Holzwarth, G., and Doty, P., 1965, The ultraviolet circular dichroism of polypeptides, J. Am. Chem. Soc. 178:350.

    Google Scholar 

  • Hormone Drugs, 1982, Proceedings of the FDA-USP Workshop on Drug and Reference Standards for Insulins, Somatropins and Thyroid-Axis Hormones (J. L. Gueriguian, E. D. Bransome, and A. S. Outschoorn, eds.), United States Phar-macopeial Convention, Rockville, Md.

    Google Scholar 

  • Houghten, R. A., Glaser, C. B., and Li, C. H., 1977, Human somatotropin reaction with hydrogen peroxide, Arch. Biochem. Biophys. 178:350.

    Article  PubMed  CAS  Google Scholar 

  • Hsu, C. C., Pearlman, R., and Curley, J. C., 1988, Some factors causing protein denaturation and aggregate formation in pharmaceutical processing, Pharm. Res. Suppl. 5:S34.

    Google Scholar 

  • Johnson, B. A., Shirokawa, J. M., Hancock, W. S., Spellman, M. W., Basa, L. J., and Aswad, D. W., 1989, Formation of isoaspartate at two distinct sites during in vitro aging of human growth hormone, J. Biol. Chem. 264:14262.

    PubMed  CAS  Google Scholar 

  • Jones, A. J. S., and O’Connor, J. V., 1982, Chemical characterization of methionyl human growth hormone, in: Hormone Drugs, Proceedings of the FDA-USP Workshop on Drug and Reference Standards for Insulins, Somatropins and Thyroid-Axis Hormones (J. L. Gueriguian, E. D. Bransome, and A. S. Outschoorn, eds.), United States Pharmacopeial Convention, Rockville, Md., pp. 335–351.

    Google Scholar 

  • Jorgensen, J. O. L., 1991, Human growth hormone replacement therapy: Pharmacological and clinical aspects, Endocr. Rev. 12:189.

    Article  PubMed  CAS  Google Scholar 

  • Jorgensen, J. O. L., Flyvbjerg, A., Lauritzen, T., Orskov, H., and Christiansen, J. S., 1988, Subcutaneous degradation of biosynthetic human growth hormone in growth hormone deficient patients, Acta Endocrinol. (Copenhagen) 118:154.

    CAS  Google Scholar 

  • Jorgensen, K. D., 1987, Comparison of the pharmacological properties of pituitary and biosynthetic human growth hormone. Demonstration of antinatriuretic/an-tidiuretic and barbital sleep effects of human growth hormone in rats, Acta Endocrinol. (Copenhagen) 114:124.

    CAS  Google Scholar 

  • Kawauchi, H., Bewley, T. A., and Li, C. H., 1976, Alkaline titrations of human somatotropin, human chorio-mammotropin and ovine prolactin by circular dichroism and fluorescence, Biochim. Biophys. Acta 446:525.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Kossiakoff, A. A., 1988, Tertiary structure is a principal determinant to protein deamidation, Science 240:191.

    Article  PubMed  CAS  Google Scholar 

  • Langley, K. E., Lai, P. H., Wypych, J., Everrett, R. R., Berg, T. F., Krabill, L. F., Davis, J. M., and Souza, L. M., 1987, Recombinant-DNA-derived bovine growth hormone from Escherichia coli 2. Biochemical, biophysical, immunological and biological comparison with pituitary hormone, Eur. J. Biochem. 163:323.

    Article  PubMed  CAS  Google Scholar 

  • Larhammar, H., Sjoholm, I., Skoog, B., and Wichman, A., 1985, Comparative conformational analysis of human somatotropin and biosynthetic methionyl human somatotropin by spectroscopic titrations, Int. J. Pharm. 23:13.

    Article  CAS  Google Scholar 

  • Lewis, U. J., Cheever, E. V., and Hopkins, W. C., 1970, Kinetic study of the deamidation of growth hormone and prolactin, Biochim. Biophys. Acta 214:498.

    Article  PubMed  CAS  Google Scholar 

  • Lewis, U. J., Singh, R. N. P., and Seavey, B. K., 1971, Human prolactin: Isolation and some properties, Biochem. Biophys. Res. Commun. 44:1169.

    Article  PubMed  CAS  Google Scholar 

  • Lewis, U. J., Peterson, S. M., Bonewald, L. F., Seavey, B. K., and VanderLaan, W. P., 1977, An interchain disulfide dimer of human growth hormone, J. Biol. Chem. 252:3697.

    PubMed  CAS  Google Scholar 

  • Lewis, U. J., Singh, R. N. P., Tutweiler, G. F., Sigel, M. B., VanderLaan, E. F., and VanderLaan, W. P., 1980, Human growth hormone: A complex of proteins, Recent Prog. Horm. Res. 36:477.

    PubMed  CAS  Google Scholar 

  • 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.

    Google Scholar 

  • Li, C. H., 1957, Properties of and structural investigations on growth hormones isolated from bovine, monkey and human pituitary glands, Fed. Proc. 16:775.

    PubMed  CAS  Google Scholar 

  • Li, C. H., 1962, Preliminary investigations on the action of pepsin on human pituitary growth hormone, J. Gen. Physiol. 45:169.

    Article  PubMed  Google Scholar 

  • Li, C. H., 1977, Bioassay of pituitary growth hormone, in: Hormonal Proteins and Peptides (C. H. Li, ed.), Academic Press, New York, pp. 2–41.

    Google Scholar 

  • Li, C. H., 1969, Aspects of the comparative chemistry of human pituitary growth hormone and chorionic somatomammotrophin, in: Growth and Growth Hormone, Proceedings of the Second International Symposium, Milan (A. Pecile and E. E. Muller, eds.), Excerpta Medica International Congress Series No. 244, pp. 17–23.

    Google Scholar 

  • Li, C. H., and Bewley, T. A., 1975, Studies on plasmin-modified growth hormone and its fragments, in: Growth Hormone and Related Peptides, Proceedings of the IIIrd International Symposium, Milan, Italy, Excerpta Medica, Amsterdam, pp. 14–32.

    Google Scholar 

  • Li, C. H., and Bewley, T. A., 1976, Human pituitary growth hormone: Restoration of full biological activity by noncovalent interaction of two fragments of the hormone, Proc. Natl. Acad. Sci. USA 73:1476.

    Article  PubMed  CAS  Google Scholar 

  • Li, C. H., and Evans, H. M., 1944, The isolation of pituitary growth hormone, Science 99:183.

    Article  PubMed  CAS  Google Scholar 

  • Li, C. H., and Graf, L., 1974, Human pituitary growth hormone: Isolation and properties of two biologically active fragments from plasmin digests, Proc. Natl Acad. Sci. USA 71:1197.

    Article  PubMed  CAS  Google Scholar 

  • Li, C. H., and Papkoff, H., 1956, Preparation and properties of growth hormone from human and monkey pituitary glands, Science 124:1038.

    Google Scholar 

  • Li, C. H., and Samuelsson, G., 1965, Human pituitary growth hormone. XI. Rate of hydrolysis by trypsin, chymotrypsin, and pepsin; effect of trypsin on the biological activity, Mol. Pharmacol 1:47.

    PubMed  CAS  Google Scholar 

  • Li, C. H., Liu, W. K., and Dixon, J. S., 1962, Human pituitary growth hormone. XII. Modified procedure for isolation and NH2-terminal amino acid sequence, Arch. Biochem. Biophys. Suppl 1:327.

    Google Scholar 

  • Li, C. H., Chung, D., Lahm, H.-W., and Stein, S., 1986, The primary structure of monkey pituitary somatotropin, Arch. Biochem. Biophys. 245:287.

    Article  PubMed  CAS  Google Scholar 

  • Li, C. H., Bewley, T. A., Chung, D., and Oosthuizen, M. M., 1987, Elephant growth hormone. Isolation and characterization, Int. J. Pept. Protein Res. 29:62.

    Article  PubMed  CAS  Google Scholar 

  • Livesey, J. H., Hodgkinson, S. C., Roud, H. R., and Donald, R. A., 1980, Effect of time, temperature and freezing on the stability of immunoreactive LH, FSH, TSH, growth hormone, prolactin and insulin in plasma, Clin. Biochem. 13:151.

    Article  PubMed  CAS  Google Scholar 

  • Lorenson, M. Y., and Jacobs, L. S., 1987, Osmotic pressure regulation of prolactin and growth hormone release from bovine secretory granules, Endocrinology 120:365.

    Article  PubMed  CAS  Google Scholar 

  • McFadden, P. N., and Clarke, S., 1982, Methylation at D-aspartyl residues in erythrocytes: Possible step in the repair of aged membrane proteins, Proc. Natl. Acad. Sci. USA 79:2460.

    Article  PubMed  CAS  Google Scholar 

  • Maddaiah, V. T., Collipp, P. J., Sharma, R. K., Chen, S. Y., and Thomas, J., 1972, Fluorescence studies of human growth hormone, Biochim. Biophys. Acta 263:133.

    Article  PubMed  CAS  Google Scholar 

  • Manning, M. C., Patel, K., and Borchardt, R. T., 1989, Stability of protein pharmaceuticals, Pharm. Res. 6:903.

    Article  PubMed  CAS  Google Scholar 

  • Markus, G., 1965, Protein substrate conformation and proteolysis, Proc. Natl. Acad. Sci. USA 54:253.

    Article  PubMed  CAS  Google Scholar 

  • Mills, J. B., Kostyo, J. L., Reagan, C. R., Wagner, S. A., Moseley, M. H., and Wil-helmi, A. E., 1980, Fragments of human growth hormone produced by digestion with thrombin: Chemistry and biological properties, Endocrinology 107:391.

    Article  PubMed  CAS  Google Scholar 

  • Milner, R. D. G., and Flodh, H. (eds.), 1985, Immunological Aspects of Human Growth Hormone, Oxford Medical Education Services.

    Google Scholar 

  • Milner, R. D., Barnes, N. D., Buckler, J. M., Carson, D. J., Hadden, D. R., Hughes, I. A., Johnston, D. I., Parkin, J. M., Price, D. A., Rayner, P. H., Savage, D. C. L., Savage, M. O., Smith, C. S., and Swift, P. G. F., 1987, United Kingdom multicentre clinical trial of somatrem, Arch. Dis. Child. 62:776.

    Article  PubMed  CAS  Google Scholar 

  • Moore, J. A., Pletcher, A., and Ross, M. J., 1986, Absorption enhancement of growth hormone from the gastrointestinal tract of rats, Int. J. Pharm. 34:35.

    Article  CAS  Google Scholar 

  • Moore, W. V., 1978, The role of aggregated human growth hormone in the therapy of human growth hormone deficient children, J. Clin. Endocrinol Metab. 46:20.

    Article  PubMed  CAS  Google Scholar 

  • Moore, W. V., and Leppert, P., 1980, Role of aggregated human growth hormone in development of antibodies to human growth hormone, J. Clin. Endocrinol. Metab. 51:691.

    Article  PubMed  CAS  Google Scholar 

  • Nederman, T., and Sjodin, L., 1987, The quantitation of human growth hormone by a radioreceptor assay using an established human cell line, J. Biol. Stand. 15:199.

    Article  PubMed  CAS  Google Scholar 

  • Nicoll, C. S., Mayer, G. L., and Russell, S. M., 1986, Structural features of prolactins and growth hormones related to their biological activity, Endocr. Rev. 7:169.

    Article  PubMed  CAS  Google Scholar 

  • Okada, Y., Taira, K., Takano, K., and Hizuka, N., 1987, A case report of growth attenuation during methionyl human growth hormone treatment, Endocrinol. Jpn. 34:621.

    Article  PubMed  CAS  Google Scholar 

  • Patel, K., and Borchardt, R. T., 1990, Deamidation of asparaginyl residues in proteins: A potential pathway for chemical degradation of proteins in lyophilized dosage forms, J. Parenteral Sci. Tech. 44:300.

    CAS  Google Scholar 

  • Patience, R. L., and Rees, L. H., 1986, Comparison of reversed-phase and anion exchange high-performance liquid chromatography for the analysis of human growth hormones, J. Chromatogr. 352:241.

    Article  PubMed  CAS  Google Scholar 

  • Pearlman, R., and Nguyen, T. H., 1989, Formulation strategies for recombinant proteins: Human growth hormone and tissue plasminogen activator, in: Therapeutic Peptides and Proteins: Formulation, Delivery and Targeting (D. Marshak and D. Liu, eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., pp. 23–31.

    Google Scholar 

  • Pearlman, R., and Nguyen, T. H., 1991, Analysis of protein drugs, in: Peptide and Protein Drug Delivery (V. H. Lee, ed.), Dekker, New York, pp. 247–301.

    Google Scholar 

  • Pearlman, R., and Nguyen, T., 1992, Pharmaceutics of protein drugs, J. Pharm. Pharmacol. 44:(Suppl.):178.

    PubMed  CAS  Google Scholar 

  • Pearlman, R., and Oeswein, J. Q., 1989, Human growth hormone formulation, European Patent Publication PCT WO 89/09614.

    Google Scholar 

  • Pearlman, R., O’Connor, B. H., and Brehm, S. L., 1987, Formulation of recombinant derived human growth hormone, 194th National Meeting of the American Chemical Society, New Orleans. Physicians Desk Reference, 46th ed., 1992, Medical Economics Company, Montvale, pp. 1049 and 1226.

    Google Scholar 

  • Pikal, M. J., Dellerman, K. M., Roy, M. L., and Riggin, R. M., 1991, The effects of formulation variables on the stability of freeze-dried human growth hormone, Pharm. Res. 8:427.

    Article  PubMed  CAS  Google Scholar 

  • Preece, M. A., and Tanner, J. M., 1976, Treatment of growth hormone deficiency, in: Proceedings of the International Congress of Paediatric Endocrinology, Bologna, Italy, Serono, 173:94.

    Google Scholar 

  • Raben, M. S., 1957, Preparation of growth hormone from pituitaries of man and monkey, Science 125:883.

    Article  PubMed  CAS  Google Scholar 

  • Rappaport, R., 1987, Preliminary results of authentic recombinant somatropin treatment in human growth hormone deficient children. French Collaborative Study, Acta Paediatr. Scand. Suppl 331:25.

    Article  PubMed  CAS  Google Scholar 

  • Reagan, C. R., Mills, J. B., Kostyo, J. L., and Wilhelmi, A. E., 1975, Biological properties of plasmin digests of S-carbamidomethylated human growth hormone, Proc. Natl. Acad. Sci. USA 72:1684.

    Article  PubMed  CAS  Google Scholar 

  • Reagan, C. R., Kostyo, J. L., Mills, J. B., Gennick, S. E., Messina, J. L., Wagner, S. A., and Wilhelmi, A. E., 1981, Recombination of fragments of human growth hormone: Altered activity profile of the recombinant molecule, Endocrinology 109:1663.

    Article  PubMed  CAS  Google Scholar 

  • Riggin, R. M., Dorulla, G. K., and Miner, D. J., 1987, A reversed-phase high-performance liquid chromatographic method for characterization of biosynthetic human growth hormone, Anal. Biochem. 167:199.

    Article  PubMed  CAS  Google Scholar 

  • Riggin, R. M., Sharr, C. J., Dorulla, G. K., Lefeber, D. S., and Miner, D. J., 1988, High-performance size-exclusion chromatographic determination of the potency of biosynthetic human growth hormone products, J. Chromatogr. 435:307.

    Article  PubMed  CAS  Google Scholar 

  • Robinson, A. B., and Rudd, C. L., 1974, Deamidation of glutaminyl and asparaginyl residues in peptides and proteins, Curr. Top. Cell Regul. 8:247.

    PubMed  CAS  Google Scholar 

  • Roongta, V., Powers, R., Jones, C., Beakage, M. J., Shields, J. E., and Gorenstein, D. G., 1989, Solution conformation of a synthetic fragment of human pituitary growth hormone. Two-dimensional NMR of an alpha-helical dimer, Biochemistry 28:1048.

    Article  PubMed  CAS  Google Scholar 

  • Roos, P., Fevold, H. R., and Gemsell, C. A., 1963, Preparation of human growth hormone by gel filtration, Biochim. Biophys. Acta 74:523.

    Article  Google Scholar 

  • Rougeot, C., Marchand, P., Dray, F., Job, J. C., Pierson, M., Ponte, C., Rochiccoili, P., and Rappaport, R., 1991, Comparative study of biosynthetic human growth hormone immunogenicity in growth hormone deficient children, Horm. Res. 35:76.

    Article  PubMed  CAS  Google Scholar 

  • Saxena, B. B., and Henneman, P. H., 1966, Isolation and properties of the electropho-retic components of human growth hormone by Sephadex-gel filtration and preparative polyacrylamide-gel electrophoresis, Biochem. J. 100:711.

    PubMed  CAS  Google Scholar 

  • Schalch, D. S., and Parker, M. L., 1964, A sensitive double antibody immunoassay for growth hormone in plasma, Nature 203:1141.

    Article  PubMed  CAS  Google Scholar 

  • Schwartz, P. L., and Batt, M., 1973, The aggregation of 125I human growth hormone in response to freezing and thawing, Endocrinology 92:1795.

    Article  PubMed  CAS  Google Scholar 

  • Sieradzki, J., Stanuch, H., Golda, W., and Szybinski, Z., 1987, Chronobiological analysis of changes in circadian rhythm of anterior pituitary hormone level during glycemia normalization by means of biostator, Horm. Metab. Res. 19:208.

    Article  PubMed  CAS  Google Scholar 

  • Singh, R. N. P., Seavey, B. K., and Lewis, U. J., 1974, Heterogeneity of human growth hormone, Endocr. Res. Commun. 1:449.

    Article  PubMed  CAS  Google Scholar 

  • Skottner, A., Forsman, A., Skoog, B., Kostyo, J. L., Cameron, C. M., Adamafio, N. A., Thorngren, K. G., and Hagerman, M., 1988, Biological characterization of charge isomers of human growth hormone, Acta. Endocrinol. (Copenhagen) 118:14.

    CAS  Google Scholar 

  • Skyler, J. S., Baumann, G., and Chrambach, A., 1977, A catalogue of isohormones of human growth hormone based upon quantitative Polyacrylamide gel electrophoresis, Acta Endocrinol. (Copenhagen) Suppl. 212:5.

    Google Scholar 

  • Teh, L. C., Murphy, L. J., Huq, N. L., Sums, A. S., Friesen, H. G., Lazarus, L., and Chapman, G. E., 1987, Methionine oxidation in human growth hormone and human chorionic somatomammotropin. Effects on receptor binding and biological activities, J. Biol. Chem. 262:6472.

    PubMed  CAS  Google Scholar 

  • Thurow, H., and Geisen, K., 1984, Stabilisation of dissolved proteins against denatur-ation at hydrophobic interfaces, Diabetologia 27:212.

    PubMed  CAS  Google Scholar 

  • USP Pharmacopeial Forum, Nov.-Dec. 1990, The United States Pharmacopeial Convention, Rockville, Md., pp. 1246–1264.

    Google Scholar 

  • Wallace, A. L. C., and Ferguson, K. A., 1961, Preparation of human growth hormone, J. Endocrinol 23:285.

    Article  PubMed  CAS  Google Scholar 

  • Welinder, B. S., Sorensen, H. H., and Hansen, B., 1987, Reversed-phase high-performance liquid chromatography of human growth hormone, J. Chromatogr. 398:309.

    Article  PubMed  CAS  Google Scholar 

  • Wetlaufer, D. B., 1962, Ultraviolet spectra of proteins and amino acids, Adv. Protein Chem. 17:303.

    Article  CAS  Google Scholar 

  • WHO Technical Report, 1975, Serial Number 565,26th Report of the World Health Organization Expert Committee on Biological Standardization, WHO, Geneva, pp. 27–28.

    Google Scholar 

  • Wilhelmi, A. E., 1961, Fractionation of human pituitary glands, Can. J. Biochem. 39:1659.

    Article  PubMed  CAS  Google Scholar 

  • Wilhelmi, A. E., 1982, Structure and function in growth hormone, in: Hormone Drugs, Proceedings of the FDA-USP Workshop on Drug and Reference Standards for Insulins, Somatropins and Thyroid-Axis Hormones (J. L. Gueriguian, E. D. Bransome, and A. S. Outschoorn, eds.), United States Pharmacopeial Convention, Rockville, Md., pp. 369–381.

    Google Scholar 

  • Winder, A. F., and Gent, W. L. G., 1971, Correction of light-scattering errors in spectrophotometric protein determination, Biopolymers 10:1243.

    Article  PubMed  CAS  Google Scholar 

  • Wright, H. T., 1991, Sequence and structure determinants of the nonenzymatic deamidation of asparagine and glutamine residues in proteins, Protein Eng. 4:283.

    Article  PubMed  CAS  Google Scholar 

  • Wu, S. L., Hancock, W. S., Pavlu, B., and Gellerfors, P., 1990, Application of high-performance hydrophobic-interaction chromatography to the characterization of recombinant DNA-derived human growth hormone, J. Chromatogr. 500:595.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Pharmaceutical Research and Development, Genentech, Inc., South San Francisco, California, 94080, USA

    Rodney Pearlman & Thomas A. Bewley

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  1. Rodney Pearlman
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  2. Thomas A. Bewley
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  1. Scios Nova, Inc., Mountain View, California, USA

    Y. John Wang

  2. Genentech, Inc., South San Francisco, California, USA

    Rodney Pearlman

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Pearlman, R., Bewley, T.A. (1993). Stability and Characterization of Human Growth Hormone. In: Wang, Y.J., Pearlman, R. (eds) Stability and Characterization of Protein and Peptide Drugs. Pharmaceutical Biotechnology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1236-7_1

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