Abstract
Increasingly, variant forms of growth hormone are being found, but an understanding of their significance has not kept pace with the ability to detect them. One of the problems is that the variants occur in much lower concentrations than the major form, thus making preparation of quantities for biologic testing a difficult task. In addition, availability of human pituitary glands for such studies was limited until recently, when clinical treatment with pituitary-derived growth hormone was discontinued and the glands became available for research projects concerned with identification of new substances. The low concentration of many of the forms raises a frequently asked question: can these forms have physiologic relevance when they occur in such small amounts compared to the major form? What is usually overlooked here is the fact that the major form occurs in an enormous quantity compared to the other pituitary hormones. A comparison of human pituitary hormones will illustrate this point. There are between 5000 and 7000 yg of the major form of human growth hormone (hGH) in a pituitary gland. If the concentration of a variant of hGH is 1% or this (50 to 70 yg), its concentration would be similar to that of FSH; a 3% concentration would equal the amount of prolactin in a gland.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Davis RB, Morris J, Ivarie R. The polypeptide P16 is a carboxy terminal cleavage product of rat growth hormone in anterior pituitary and GH- pituitary tumor cells. Mol Endocrinol 1987; 1: 102.
Sinha YN, Gilligan TA. A “20K” form of growth hormone in the murine pituitary gland. Proc Soc Exp Biol Med 1984; 177: 465.
Yokoya A, Friensen HG. Human growth hormone (GH)-releasing factor stimulates and somatostatin inhibits the release of rat GH variants. Endocrinology 1986; 119: 2097.
Seeburg PH. The human growth hormone gene family: nucleotide sequences show recent divergence and predict a new polypeptide hormone. DNA 1982; 1: 239.
Frankenne F, Rentier-Delrue F, Scippo M-L, Martial J, Hennen G. Expression of the growth hormone variant gene in human placenta. J Clin Endocrinol Me tab 1987; 64: 635.
Chien Y-H, Thompson EB. Genomic organization of rat prolactin and growth hormone genes. Proc Natl Acad Sci USA 1980; 77: 4583.
DeNoto FM, Moore DD, Goodman HM. Human growth hormone DNA sequence and mRNA structure: possible alternative splicing. Nucleic Acids Res 1981; 9: 3719.
Wallis M. Growth hormone: deletions in the protein and introns in the gene. Nature 1980; 284: 512.
Lewis UJ, Bonewald LF, Lewis LJ. The 20,000-dalton variant of human growth hormone: location of the amino acid deletion. Biochem Biophys Res Commun 1980; 92: 511.
Baumann G, MacCart JG, Ambrun K. The molecular nature of circulating growth hormone in normal and acromegalic man: evidence for a principal and minor monomeric form. J Clin Endocrinol Metab 1983; 56: 946.
Sinha YN, Gilligan TA, Lee DW, Baxi SC, VanderLaan WP. Demonstration of 20K growth hormone in human plasma by gel electrophoretic-immuno- staining-autoradiographic assay (GEISAA). Horm Metab Res 1986; 18: 402.
Markoff E, Lee DW, Culler FL, Jones KL, Lewis UJ. Release of the 22,000- and the 20,000-dalton variants of growth hormone in vivo and in vitro by human anterior pituitary cells. J Clin Endocrinol Metab 1986; 62: 664.
Hampson RK, Rottman FM. A potential variant of bovine growth hormone resulting from non-splicing of an intron. Fed Proc 1986; 45: 1703.
Singh RNP, Seavey BK, Rice VP, Lindsey TT, Lewis UJ. Modified forms of human growth hormone with increased biological activities. Endocrinology 1974; 94: 883.
Yadley RA, Chrambach A. Isohormones of human growth hormone. II. Plasmin-catalyzed transformation and increase in prolactin biological activity. Endocrinology 1973; 93: 858.
Singh RNP, Seavey BK, Lewis LJ, Lewis UJ. Human growth hormone peptide 1–43: isolation from pituitary glands. J Prot Chem 1983; 2: 425.
Frigeri LG, Teguh K, Wehrenberg WB, Ling N, Lewis UJ. Enhancement of insulin action by NH-terminal peptides of growth hormone [Abstract]. Clin Res 1986; 34: 103A.
Frigeri LG, Ling N, Rudman C, VanderLaan WP, Lewis UJ. Increased in vivo glucose utilization by amino terminal peptides of growth hormone [Abstract]. Burlington, Vermont: Research Symposium of Diabetes and Exercise, July, 1983.
Lewis UJ, Peterson SM, Bonewald LF, Seavey BK, VanderLaan WP. An interchain disulfide dimer of human growth hormone. J Biol Chem 1977; 252: 3697.
Benveniste R, Stachura ME, Szabo M, Frohman LA. Big growth hormone (GH): conversion to small GH without peptide bond cleavage. J Clin Endocrinol Metab 1975; 41: 422.
Schneider AB, Kowalski K, Russell J, Sherwood LM. Identification of the interchain disulfide bonds of dimeric human placental lactogen. J Biol Chem 1979; 254: 3782.
Tokunaga T, Tanaka T, Ikehara M, Ohtsuka E. Synthesis and expression of a human growth hormone (somatotropin) gene mutated to change cysteine-165 to alanine. Eur J Biochem 1985; 153: 445.
Dixon JS, Li CH. Retention of the biological potency of human pituitary growth hormone after reduction and carbamidomethylation., Science 1966; 154: 785.
Lewis UJ, Singh RNP, Bonewald LF, Seavey BK. Altered proteolytic cleavage of human growth hormone as a result of deamidation. J Biol Chem 1981; 256: 1 1645.
Lewis UJ, Singh RNP, Bonewald LF, Lewis LJ, VanderLaan WP. Human growth hormone: additional members of the complex. Endocrinology 1979; 104: 1256.
Liberti JP, Antoni BA, Chlebowski JF. Naturally-occurring pituitary growth hormone is phosphorylated. Biochem Biophys Res Commun 1985; 128: 713.
Oetting WS, Tuazon PT, Traugh JA, Walker AM. Phosphorylation of prolactin. J Biol Chem 1986; 261: 1649.
Sinha YN, Lewis UJ. A lectin-binding immunoassay indicates a possible glycosylated growth hormone in the human pituitary gland. Biochem Biophys Res Commun 1986; 140: 491.
Lewis UJ, Singh RNP, Lewis LJ, Seavey BK, Sinha YN. Glycosylated ovine prolactin. Proc Natl Acad Sci USA 1984; 81: 385.
Pankov YuA, Butnev VYu. Multiple forms of pituitary prolactin. Glycosylated form of prolactin with enhanced biological activity. Int J Pept Protein Res 1986; 28: 113.
Meuris S, Svoboda M, Christophe J, Robyn C. Evidence for a glycosylated prolactin variant in human pituitary and amniotic fluid. In: MacLeod RM, Thorner MO, Scapagnini U, eds. Prolactin, basic and clinical correlates. Padova: Livana Press, 1985: 487 – 93.
Lewis UJ. Variants of growth hormone and prolactin and their post- translational modifications. Annu Rev Physiol 1984; 46: 33.
Laemmli UK. Cleavage of structural proteins during assembly of the head of bacteriophage T. Nature 1970; 227: 680.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Plenum Press, New York
About this chapter
Cite this chapter
Lewis, U.J., Singh, R.N.P., Lewis, L.J., Abadi, N. (1988). Multiple Forms of Growth Hormone. In: Bercu, B.B. (eds) Basic and Clinical Aspects of Growth Hormone. Serono Symposia, USA. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5505-2_4
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5505-2_4
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5507-6
Online ISBN: 978-1-4684-5505-2
eBook Packages: Springer Book Archive