A naturally occurring structural variant of human growth hormone

U. J. Lewis, J. T. Dunn, L. F. Bonewald, B. K. Seavey, W. P. Vanderlaan

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166 Scopus citations


A structural variant of human growth hormone was isolated from pituitary extracts. The newly recognized modification had a molecular weight of 20,000 when analyzed by electrophoresis in sodium dodecyl sulfate, whereas human growth hormone gave a value near 22,000. By isoelectric focusing the variant had a pI of 5.85; human growth hormone had a value of 5.6. All extracts of 30 individual fresh frozen pituitary glands, analyzed by electrophoresis in sodium dodecyl sulfate, contained the 20,000-dalton component. The amount was estimated to be between 5 and 10% of the growth hormone in the extract. Amino acid composition of the 20,000-dalton variant showed about 10 fewer amino acids than in growth hormone. Structure studies indicated that the difference between the variant and human growth hormone was probably in the region of residues 39 to 64. There could also be differences in the region of 24 to 38 and 159 to 167, but the results were inconclusive. The first 23 residues of the 20,000-dalton form were identical with those found in human growth hormone and 17 corresponding tryptic peptides of the two forms had identical amino acid compositions. Phenylalanine was the COOH-terminal amino acid and glycine was in the penultimate position in both forms. The 20,000-dalton form remained intact after reduction with 2-mercaptoethanol. We conclude that the 20,000-dalton form is a structural variant of growth hormone. An unusual property of the 20,000-dalton variant was that it reacted rather poorly with antibody to human growth hormone even though it had good growth promoting properties. The variant was only about one-third as active as growth hormone in a radioimmunoassay, yet by the body weight gain assay in hypophysectomized rats, the substance had a mean potency of 1.5 IU/mg. The results indicate that the human pituitary gland produces an active form of growth hormone that may not be accurately detected by current radioimmunoassays.

Original languageEnglish (US)
Pages (from-to)2679-2687
Number of pages9
JournalJournal of Biological Chemistry
Issue number8
StatePublished - 1978
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lewis, U. J., Dunn, J. T., Bonewald, L. F., Seavey, B. K., & Vanderlaan, W. P. (1978). A naturally occurring structural variant of human growth hormone. Journal of Biological Chemistry, 253(8), 2679-2687.