Hormonal Glycoproteins

Studies on the sub-units of human glycoprotein hormones in relation to reproduction have been reviewed. One volume of a treatise on hormonal proteins and peptides has been devoted to thyroid hormones. The ectopic production of human chorionic gonadotrophin (hCG) and its a- and /J-sub-units has been discussed.  

Feller, D. Behnke, and E. Gruenstein, Bioc/j/m. Biophys. Acta, 1979, 586, 315. 

Franchimont, A. Reuter, and U. Gaspard, in Current Topics in Experimental Endocrinology , ed. L. Martini and V. H, T. James, Academic Press, New York, 1978, Vol. 3. 

Carbohydrate Chemistry carbohydrate units of animal glyco- 

The precise location and structure (26) of the four 0-glycosidically-linked oligosaccharide units in the C-terminal peptide of )3-sub-unit chains of human chorionic gonadoptrophin and a revised amino-acid sequence for this peptide have been reported. 

Reviews of the experimental methods used in hormone research have been published. One volume is concerned with steroid hormones, and includes references to steroid-binding glycoproteins in sera and to cytoplasmic receptors. A second volume deals with the methodology associated with peptide hormones, including procedures for tritium-labelling of sialylated glycoproteins. A 

Leblond-Larouche, R. Morals, V. N. Nigam, and S. Karasaki, Arch. Biochem. Biophys., 1975, 167, 1. 

Desialylated human chorionic gonadotrophin was found to be twice as effective as the native hormone in competing for the binding site of receptors in rat testis. However, it has been pointed out that caution must be exercised when radio-ligand receptors are used to assay preparations of human chorionic gonadotrophin of different sialic acid contents. 

The chemistry, biology, immunology, biochemistry, and clinical chemistry of the gonadotrophins have been comprehensively reviewed several sections deal specifically with the structures and functions of the carbohydrate moieties of gonadotrophins.  

Polyacrylamide gel electrophoresis has been used to separate five active thyrotrophins from human pituitary glands. Treatment of each thyrotrophin with neuraminidase afforded more basic components without change in the overall pattern, supporting the view that differences between them cannot be attributed to variations in the sialic acid contents. 

The chemistry of the gonadotrophins, particularly the biological roles of sialy-lation and desialylation and the excretion of subunits from placental and pituitary tissues, has been reviewed. Aspects of the chemistry, physiology, and assay of prolactin have been discussed.  

A degree of homology has been established among the sequences of amino-acids located at the NHj-terminus of the p-subunit of cholera toxin and those in human chorionic gonadotrophin, thyrotrophin, and luteinizing and follicle-stimulating hormones.  

380 Prolactin , Annual Research Reviews, ed. D. F. Horrobin, Eden Press, Montreal, 1976. 

Five active components obtained from human pituitary thyrotrophin by polyacrylamide gel electrophoresis have similar amino-acid and carbohydrate compositions all of them contain residues of L-fucose, D-mannose, D-galactose, 2-amino-2-deoxy-D-galactose, 2-amino-2-deoxy-D-gIucose, and sialic acid. Bovine and whale thyrotrophins have been purified by affinity chromatography on immobilized concanavalin A.  

Elucidation of the sequence of amino-acids in a fragment (residues 115—145) from the COjH-terminus of the P-subunit of human chorionic gonadotrophin showed that carbohydrate components are attached to serine-121, -127, -132, and -138 3 Yjig sequence of the amino-acids 109—145 has been determined independently.  

The processing of placental peptide hormones synthesized in lysates containing membranes derived from tunicamycin-treated ascites tumour cells has been reported. The cleavage of a pre-glycoprotein, pre-human chorionic gonadotrophin, and the sequestration of the processed form within the membranes, occurs in the absence of glycosylation. Thus, in contrast to certain processing 

Concanavalin A has been reported to stimulate the secretion of human chorionic gonadotrophin by human choriocarcinoma cells. Since the stimulation is thought to occur subsequent to interactions at the membrane level, concanavalin A may be used as a probe for studying membrane-related events in the control of the secretion of this hormone. 

Structural analyses of the L-asparagine-1 inked (33) and L-serine-linked (34) oligosaccharide chains of human chorionic gonadotrophin have been performed.  

The L-asparagine-linked oligosaccharide chains of the a- and )3-sub-units have similar general structures but in addition the jS-unit has one residue of L-fucose, which may be linked to a o-galactosyl or a 2-acetamido-2-deoxy-D-glucosyl unit. Sequential removal of sugar residues from the hormone markedly diminishes its ability to stimulate the accumulation of cyclic AMP by porcine granulosa cells.  

A common structure (35) has been proposed for the oligosaccharide moieties of glycopeptides isolated from the a-subunits of human follitropin, lutropin, and thyrotropin. Microheterogeneity amongst the glycopeptides is thought to be due to variations in the number of terminal neuraminic acid and L-fucosyl groups. 

Hormone receptors and their assay, structure, and function have been reviewed. Chromatography on Sepharose-concanavalin A has been used to measure the concentration of glycoprotein hormones in human plasma.  

A simple radioactive assay has been developed to evaluate the combination of subunits from human chorionic gonadotrophin (hCG), thyrotrophin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The method is claimed to detect the formation of less than one picomole of the resulting hormone. An homology in the amino-acid sequences has been detected in the B-chain of cholera toxin and the /S-subunits of thyrotrophin, LH, hCG, and FSH, and is thought to represent the site on these proteins that binds to the receptors on membranes. Hybridization studies using the a- and -subunits of thyrotrophin, lutrophin, and CG from different species e.g. sheep, cattle, and humans) demonstrated increases in the a-helix and -sheet contents of the proteins, comparable to those observed in the thyrotrophin subunit assembly.  

Frieden, Chemical Endocrinology , Academic Press, New York, San Francisco, and 

Pernollet, J. Gamier, J. G. Pierce, and R. Salesse, Biochim. Biophys. Acta, 1976, 446, 

Porcine FSH has been found to contain 2.1% of sialic acid.  

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HIV viral entry inhibitors, CCR5 and CXCR4, 42, 301 homeobox genes, 27, 227 hormones, glycoprotein, 12, 211 hormones, non-steroidal, 1,191 3,184... 

Anterior pituitary Thyrotropin (TSH) Luteinizing hormone Glycoproteins... 

Fig. 2. Generalized structure of N-linked oligosaccharide of the pituitary glycoprotein hormones. SO = sulfate, GIcNAc = N — acetylglucosamine, GalNAc = N — acetylgalactosamine, Man = mannose, Fuc = fucose, SA = sialic (neuraminic) acid.

Thyroid Hormones. Iodine, absorbed as P, is oxidized in the thyroid and bound to a thyroglobulin. The resultant glycoprotein, mol wt 670,000, contains 120 tyrosine residues of which ca two-thirds are available for binding iodine in several ways. Proteolysis introduces the active hormones 3,5,3 -triiodothyronine (T ) and 3,5,3, 5 -tetraiodothyronine (T, (thyroxine) in the ratio Ty.T of 4 1 (121,122). 

Inhibin and Activin. Inhibin, a water-soluble, gonadal factor known for over 50 years to inhibit pituitary function, has been isolated and identified (127—130). Inhibin is a glycoprotein hormone that preferentially inhibits the secretion of FSH. It consists of an a-chain subunit, mol wt 14,000, linked by disulfide bonds to a P-chain subunit, mol wt 18,000. There exist two forms of the P-chain subunit, P-A and P-B. The smaller subunit combines with either the P-A or P-B subunit to form inhibin-A or inhibin-B, respectively. 

Chorionic gonadotropin (CG) is produced in the placenta. Together- with the pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), it constitutes the glycoprotein family of gonadotropins. The actions of CG are mediated by the LH receptor, both belonging to the superfamily of G-protein Coupled Receptors. 

Anemia may occur in patients with chronic renal failure as tlie result of the inability of the kidney to produce erythropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia Two examples of drug used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp). 

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