Influence of carbohydrates on the antigenic structure of gonadotropins: distinction of agonists and antagonists

The carbohydrate-deficient glycoprotein syndrome (CDGS) is a developmental disease associated with an abnormally high isoelectric point of serum transferrin. Carbohydrate analyses of this glycoprotein initially suggested a defect in N-linked oligosaccharide processing, although more recent studies indicate a defect in the attachment of these sugar chains to the protein. We studied both serum glycoproteins and fibroblast-derived [2-3H]mannose-labeled oligosaccharides from CDGS patients and normal controls. While there was a decrease in the glycosylation of serum glycoproteins of affected individuals, differences were not seen in either monosaccharide composition or oligosaccharide structures. The lectin-binding profiles of glycopeptides from [2-3H]-mannose-labeled fibroblasts were likewise indistinguishable. However, the incorporation of [2-3H]mannose into both glycoproteins and the dolichol-linked oligosaccharide precursor was significantly reduced. Thus, at least in some patients, CDGS is not due to a defect in processing of N-linked oligosaccharides, but rather to defective synthesis and transfer of nascent dolichol-linked oligosaccharide precursors. This abnormality could result in both a failure to glycosylate some sites on some proteins, as well as secondary abnormalities in overall glycoprotein processing and/or function. (J.

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“…4). (53), and suggests a plausible hypothesis for the hypogonadism reported in some cases of CDGS (7, 9, 54).…”

Section: Discussionmentioning

confidence: 97%

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

Powell¹,

Paneerselvam²,

Vij³

et al. 1994

J. Clin. Invest.

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“…Naturally occurring isoforms of pitu¬ itary TSH, separated by gel isoelectrofocusing, also differ in their ability to stimulate cAMP release and thymidine incorporation into DNA ). The type and extent of glycosylation influ¬ ences the antigenic structure of these glycoproteins (Sairam et al 1990). …”

Section: Introductionmentioning

confidence: 99%

Different isoforms of human pituitary thyroid-stimulating hormone have different relative biological activities

Pickles

Peers²,

Robertson³

et al. 1992

Journal of Molecular Endocrinology

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The relationship between the immunological and biological activities of thyroid-stimulating hormone (TSH) isoforms present in the three human pituitary preparations 68/38 (1st IRP), 80/558 (2nd IRP) and 63/14 (MRC Research Standard A) was investigated. The isoforms were separated by chromatofocusing. Six peaks of immunoactivity were detected in 80/558, with pI values (means +/- S.E.M.) of 6.6 +/- 0.1, 6.2 +/- 0.1, 5.9 +/- 0.1, 5.5 +/- 0.1, 5.2 +/- 0.1 and 4.9 +/- 0.1. Four peaks, with pI values of 6.8 +/- 0.1, 5.9 +/- 0.1, 5.5 +/- 0.1 and 5.2 +/- 0.1, were observed for 68/38. Standard 63/14 had five peaks, with pI values of 6.9 +/- 0.1, 6.4 +/- 0.1, 5.9 +/- 0.1, 5.4 +/- 0.1 and 4.9 +/- 0.1. For each standard, six fractions around the peak areas and at the top and bottom of the gradient were pooled and microconcentrated to < 1.0 ml. Microconcentrated TSH samples were assayed in three TSH bioassays based upon FRTL-5 thyroid cells, utilizing cyclic AMP accumulation, iodide and thymidine uptake as end-points and standard 80/558 as reference preparation. The more acidic forms of TSH showed a higher biological:immunological (B:I) ratio for cyclic AMP accumulation with, for example, 63/14 having a maximum of 3.7 (pI 4.9) and a minimum of < 0.7 (pI 6.9). In contrast, the maximum and minimum B:I ratios for iodide uptake for 63/14 were 3.8 (pI 6.9) and < 0.8 (pI 4.6), and for thymidine uptake, maximum and minimum ratios were 7.2 (pI 6.9) and 1.1 (pI 4.6) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…This heterogeneity relates to the composition of the carbohydrate moiet¬ ies (Baenziger & Green, 1988), and the biological activity of these molecules is closely related to the extent of glycosylation, especially the sialic acid resi¬ dues (Berman et al 1985;Amir et al 1987;Keel, 1989). Furthermore, the type and extent of glycosyl¬ ation also appears to influence the antigenic structure of the secreted glycoproteins (Sairam et al 1990). The existence of microheterogeneity has been well documented for LH and to a lesser extent for FSH.…”

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confidence: 99%

Microheterogeneity of thyroid-stimulating hormone from the pituitaries of euthyroid, hypothyroid and hyperthyroid rats

Pickles

Peers²,

Robertson³

et al. 1992

Journal of Molecular Endocrinology

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The microheterogeneity of pituitary thyroid-stimulating hormone (TSH) is dependent on variations in the hormone's carbohydrate moieties. In this study, changes in the pattern of heterogeneity have been assessed by chromatofocusing, which separates the isospecies on the basis of their isoelectric points (pI). Rats (n = 6 per group) were either untreated or rendered hypo- or hyperthyroid by including in the drinking water either propylthiouracil (0.05% for 8 weeks) or thyroxine (T4; 4 mg/l for 6 weeks) before they were killed at 16 weeks. On autopsy, serum TSH and total T4 were (means +/- S.E.M.): 2 +/- 0.3 micrograms TSH/l and 64 +/- 5 nmol T4/l (control); < 1 microgram TSH/l and 133 +/- 6 nmol T4/l (hyperthyroid); 58 +/- 6 micrograms TSH/l and 32 +/- 6 nmol T4/l (hypothyroid). The pituitaries were individually homogenized and the TSH isoforms separated by chromatofocusing over a pH range of 7-4. Fractions were assayed for TSH by radioimmunoassay. TSH from the control group was distributed into seven major peaks with pI values of (means +/- S.E.M., n = 6) 6.9 +/- 0.1, 6.6 +/- 0.1, 6.2 +/- 0.1, 5.8 +/- 0.1, 5.5 +/- 0.1, 5.2 +/- 0.1 and 4.8 +/- 0.1; 7 +/- 3% of the TSH had a pI of < 4.0. Six peaks of TSH were conserved in the hypothyroid group (with pI values of 6.8 +/- 0.1, 6.5 +/- 0.1, 6.2 +/- 0.1, 5.8 +/- 0.1, 5.4 +/- 0.1 and 5.2 +/- 0.1), and 11 +/- 4% of the hormone had a pI of < 4.0.(ABSTRACT TRUNCATED AT 250 WORDS)

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Influence of carbohydrates on the antigenic structure of gonadotropins: distinction of agonists and antagonists

Cited by 19 publications

References 15 publications

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

Different isoforms of human pituitary thyroid-stimulating hormone have different relative biological activities

Microheterogeneity of thyroid-stimulating hormone from the pituitaries of euthyroid, hypothyroid and hyperthyroid rats

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