Abstract
There appears to be only a single gene for the gonadotropin α-subunit in humans (1, 2), but the α polypeptide may combine noncovalently with any of several β-subunits to form one of the heterodimeric hormones, LH, FSH, TSH or hCG. Less commonly appreciated is the notion that substantial quantities of α are secreted in uncombined or “free α” forms.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Fiddes JC, Goodman HM. Isolation, cloning and sequence analysis of the cDNA for the α-subunit of human chorionic gonadotropin. Nature 1980; 281: 351–6.
Boothby M, Ruddon RW, Anderson C, McWilliams D, Boime I. A single gonadotropin α-subunit gene in normal tissue and tumor-derived cell lines. J Biol Chem 1981; 256: 5121–7.
Ashitaka Y, Nishimura R, Futamura K, Ohashi M, Tojo S. Serum and chorionic tissue concentrations of human chorionic gonadotropin and its subunits during pregnancy. Endocrinol Jpn 1974; 21: 547–50.
Reuter AM, Gaspard UJ, Deville JL, Vrindts-Gevaert Y, Franchimont P. Serum concentrations of human chorionic gonadotrophin and its alpha and beta subunits. Clin Endocrinol 1980; 13: 305–17.
Wehmann RE, Nisula BC. Metabolic clearance rates of the subunits of human chorionic gonadotropin in man. J Clin Endocrinol Metab 1979; 48: 753–9.
Wehmann RE, Nisula BC. Metabolic and renal clearance rates of purified human chorionic gonadotropin. J Clin Invest 1981; 68: 184–94.
Blithe DL, Nisula BC. Similarity of the clearance rates of free a-subunit and a-subunit dissociated from intact human chorionic gonadotropin, despite differences in sialic acid contents. Endocrinology 1987; 121: 1215–20.
Ozturk M, Brown N, Milunsky A, Wands J. Physiological studies of human chorionic gonadotropin and free subunits in the amniotic fluid compartment compared to those in maternal serum. J Clin Endocrinol Metab 1988; 67: 1117–21.
Blithe DL, Nisula BC. Variations in the oligosaccharides on free and combined alpha subunits of human choriogonadotropin in pregnancy. Endocrinology 1985; 117: 2218–28.
Kessler MJ, Reddy MS, Shah RH, Bahl OP. Structures of N-glycosidic carbohydrate units of human chorionic gonadotropin. J Biol Chem 1979; 254: 7901–8.
Fein HG, Rosen SW, Weintraub BD. Increased glycosylation of serum hCG and subunits from eutopic and ectopic sources: comparison with placental and urinary forms. J Clin Endocrinol Metab 1980; 50: 1111–20.
Posillico EG, Handwerger S, Tyrey L. Demonstration of intracellular and secreted forms of large human chorionic gonadotrophin alpha subunit in cultures of normal placental tissue. Placenta 1983; 4: 439–48.
Blithe DL. Carbohydrate composition of the alpha subunit of human choriogonadotropin and the free alpha molecules produced in pregnancy: most free alpha and some combined hCG-alpha molecules are fucosylated. Endocrinology 1990; 126: 2788–99.
Kornfeld R, Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem 1985; 54: 631–64.
Schachter H. Biosynthetic controls that determine the branching and micro-heterogeneity of protein-bound oligosaccharides. Biochem Cell Biol 1986; 64: 163–81.
Weishaar G, Hiyama J, Renwick AGC. Site-specific N-glycosylation of human chorionic gonadotropin: structural analysis of glycopeptides by one-and two-dimensional 1H NMR spectroscopy. Glycobiology 1991; 1: 393–404.
Tabas I, Kornfeld S. The synthesis of complex-type oligosaccharides: identification of an α-D-mannosidase activity in a late stage of processing of complex-type oligosaccharides. J Biol Chem 1978; 253: 7779–86.
Harpaz H, Schachter H. Control of glycoproteiin synthesis: bovine colostrum UDP-N-acetylglucosamine: α-D-mannoside β2-N-acetylglucosaminyltransferase I. Separation from UDP-N-acetylglucosamine: α-D-mannoside β2-Nacetylglucosaminyltransferase II, partial purification and substrate specificity. J Biol Chem 1980; 255: 4885–93.
Longmore GD, Schachter H. Product-identification and substrate-specificity studies of the GDP-L-fucose: 2-acetamido-2-deoxy-β-D-glucoside (Fuc goes to Asn-linked G1cNAc) 6-α-L-fucosyltransferase in a Golgi-rich fraction from porcine liver. Carbohydr Res 1982; 100: 365–92.
Corless CL, Bielinska MB, Ramabhadran TV, et al. Gonadotropin a subunit: differential processing of free and combined forms in human trophoblast and transfected mouse cells. J Biol Chem 1987; 262: 14197–203.
Parsons TF, Pierce JG. Free α-like material from bovine pituitaries: removal of its O-linked oligosaccharide permits combination with lutropin-β. J Biol Chem 1984; 259: 2662–6.
Benveniste R, Conway MC, Puett D, Rabinowitz D. Heterogeneity of the human chorionic gonadotropin α-subunit secreted by cultured choriocarcinoma (JEG) cells. J Clin Endocrinol Metab 1979; 48: 85–91.
Tulsiani DRP, Harris TM, Touster O. Swainsonine inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi Mannosidase II. J Biol Chem 1982; 257: 7936–9.
Kang MS, Elbein AD. Alterations in the structure of the oligosaccharides of vesicular stomatitis virus G protein by Swainsonine. J Virol 1983; 46: 60–9.
Blithe DL. N-linked oligosaccharides on free alpha interfere with its ability to combine with human chorionic gonadotropin-beta subunit. J Biol Chem 1990; 265: 21951–6.
Skarulis MC, Wehmann RE, Nisula BC, Blithe DL. Glycosylation changes in human chorionic gonadotropin and free alpha subunit as gestation progresses. J Clin Endocrinol Metab 1992; 75: 91–6.
Kornfeld R, Ferris C. Interaction of immunoglobulin glycopeptides with Concanavalin A. J Biol Chem 1975; 250: 2614–9.
Kornfeld K, Reitman ML, Kornfeld R. The carbohydrate binding specificity of pea and lentil lectins: fucose is an important determinant. J Biol Chem 1981; 256: 6633–40.
Canfield RE, Morgan FJ, Kammerman S, Bell JJ, Agnosto GM. Studies of human chorionic gonadotropin. Recent Prog Horm Res 1971; 27: 121–64.
Blithe DL, Richards RG, Skarulis MC. Free alpha molecules from pregnancy stimulate secretion of prolactin from human decidual cells: a novel function for free alpha in pregnancy. Endocrinology 1991; 129: 2257–9.
Tyson JE, Hwang P, Guyda H, Friesen HG. Studies of prolactin secretion in human pregnancy. Am J Obstet Gynecol 1972; 113: 14–20.
Clements JA, Reyes FI, Winter JSD, Faiman C. Studies on human sexual development, IV. Fetal pituitary and serum, and amniotic fluid concentrations of prolactin. J Clin Endocrinol Metab 1977; 44: 408–13.
Begeot M, Hemming FJ, Dubois PM, Combarnous Y, Dubois PM, Aubert ML. Induction of pituitary lactotrope differentiation by luteinizing hormone a subunit. Science 1984; 226: 566–8.
Begeot M, Hemming FJ, Martinat N, Dubois MP, Dubois PM. Gonadotropin releasing hormone (GnRH) stimulates immunoreactive differentiation of pituitary lactotropes. Endocrinology 1983; 112: 2224–6.
Spratt DI, Chin WW, Ridgway EC, Crowley WF. Administration of low dose pulsatile gonadotropin-releasing hormone to GnRH-deficient men regulates free alpha-subunit secretion. J Clin Endocrinol Metab 1986; 62: 102–8.
Handwerger S, Harmon I, Costello A, Markoff E. Cyclic AMP inhibits the synthesis and release of prolactin from human decidual cells. Mol Cell Endocrinol 1987; 50: 99–106.
Sinha YN, Selby FW, Lewis UJ, Vanderlaan WP. A homologous radioimmunoassay for human prolactin. J Clin Endocrinol Metab 1973; 36: 509–16.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Springer-Verlag New York, Inc.
About this paper
Cite this paper
Blithe, D.L. (1994). Structure and Function of the Gonadotropin Free α Molecule of Pregnancy. In: Lustbader, J.W., Puett, D., Ruddon, R.W. (eds) Glycoprotein Hormones. Serono Symposia USA. Springer, New York, NY. https://doi.org/10.1007/978-1-4613-8386-4_14
Download citation
DOI: https://doi.org/10.1007/978-1-4613-8386-4_14
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4613-8388-8
Online ISBN: 978-1-4613-8386-4
eBook Packages: Springer Book Archive