Role of carbohydrate of human chorionic gonadotropin in the mechanism of hormone action

Moyle, W. R.; Bahl, O P; März, Leopold

doi:10.1016/s0021-9258(19)40704-7

Cited by 240 publications

(16 citation statements)

References 20 publications

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“…By comparison, phTSH, which physiologically occurs in a variety of glycosylation isoforms, terminates both in SO 4 -4GalNAc␤1-4GlcNAc␤1-2Man␣ and Sia␣2-3Gal␤1-4GlcNAc-␤1-2Man␣ as described by Green and Baenziger (2). Interestingly, enzymatic removal of terminal sialic acid residues of rhTSH increased the in vitro bioactivity of the hormone (17) similar to findings for recombinant bovine LH (15), but unlike for hCG, in which sequential deglycosylation resulted in a stepwise reduction of activity (18). These findings suggested that the role of the oligosaccharides may be different for hTSH compared with hCG and hFSH.…”

supporting

confidence: 63%

“…It had previously been reported that the weak thyrotropic activity of hCG (for review, see Ref. 39), which has recently been linked to a direct interaction with the rhTSH receptor (31,40,41), increased upon desialylation (42), in contrast to a decrease at its native receptor (18). When we tested the thyrotropic activity of CHO-K1-expressed hCG site-specifically deglycosylated at the ␣ subunit, we observed an increase of activity of ␣Q52/hCG␤ but not of ␣Q78/hCG␤.…”

Section: Discussionmentioning

confidence: 99%

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Expression of Human Thyrotropin in Cell Lines with Different Glycosylation Patterns Combined with Mutagenesis of Specific Glycosylation Sites

Grossmann

Szkudlinski

Tropea

et al. 1995

Journal of Biological Chemistry

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We used a novel approach to study the role of the Asn-linked oligosaccharides for human thyrotropin (hTSH) activity. Mutagenesis of Asn (N) within individual glycosylation recognition sequences to Gln (Q) was combined with expression of wild type and mutant hTSH in cell lines with different glycosylation patterns. The in vitro activity of hTSH lacking the Asn alpha 52 oligosaccharide (alpha Q52/TSH beta) expressed in CHO-K1 cells (sialylated oligosaccharides) was increased 6-fold compared with wild type, whereas the activities of alpha Q78/TSH beta and alpha/TSH beta Q23 were increased 2-3-fold. Deletion of the Asn alpha 52 oligosaccharide also increased the thyrotropic activity of human chorionic gonadotropin, in contrast to previous findings at its native receptor. The in vitro activity of wild type hTSH expressed in CHO-LEC2 cells (sialic acid-deficient oligosaccharides), CHO-LEC1 cells (Man5GlcNAc2 intermediates), and 293 cells (sulfated oligosaccharides) was 5-8-fold higher than of wild type from CHO-K1 cells. In contrast to CHO-K1 cells, there was no difference in the activity between wild type and selectively deglycosylated mutants expressed in these cell lines. Thus, in hTSH, the oligosaccharide at Asn alpha 52 and, specifically, its terminal sialic acid residues attenuate in vitro activity, in contrast to the previously reported stimulatory role of this chain for human chorionic gonadotropin and human follitropin activity. The increased thyrotropic activity of alpha Q52/CG beta suggests that receptor-related mechanisms may be responsible for these differences among the glycoprotein hormones. Despite their increased in vitro activity, alpha Q52/TSH beta, and alpha Q78/TSH beta from CHO-K1 cells had a faster serum disappearance rate and decreased effect on T4 production in mice. These findings highlight the importance of individual oligosaccharides in maintaining circulatory half-life and hence in vivo activity of hTSH.

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supporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Expression of Human Thyrotropin in Cell Lines with Different Glycosylation Patterns Combined with Mutagenesis of Specific Glycosylation Sites

Grossmann

Szkudlinski

Tropea

et al. 1995

Journal of Biological Chemistry

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“…The role of glycosylation in activation of these receptors is somewhat perplexing. Although deglycosylated hCG binds to the receptor with high affinity, its activation of cAMP production is gradually attenuated on removal of sugar moieties [61], with greatest sensitivity to glycosylation at Asn52(a) [62]. In our model of the complex, this residue is at the opposite end to other sites implicated in transmembrane activation.…”

Section: Mutagenesis Of the Hormonesmentioning

confidence: 89%

Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone–receptor interactions

Jiang

Dréano²,

Buckler³

et al. 1995

Structure

180

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The predicted models for the structures and mode of hormone binding of the glycoprotein hormone receptors are to a large extent consistent with currently available biochemical and mutational data. Repeated sequences in beta-barrel proteins are shown to have general implications for constraints on structure. Averaging techniques used here to recognize the structural motif in these receptors should also apply to other proteins with repeated sequences.

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“…Our knowledge of IVF outcomes with a GnRHa trigger has been mostly through studies that have focused on ways to decrease OHSS. The conventional hCG trigger is prone to OHSS because it is supraphysiologic in half life and activity (108). As a result, the hCG trigger is more profoundly luteotropic, thereby increasing the risk for OHSS.…”

Section: Gnrha Triggermentioning

confidence: 99%

Regimen of ovarian stimulation affects oocyte and therefore embryo quality

Bosch

Labarta

Kolibianakis

et al. 2016

Fertility and Sterility

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Without any doubt the regimen used to mature multiple capable oocytes for IVF impacts IVF outcomes. Studies have indicated that the inclusion of LH activity, adjuvant agents such as growth hormone (GH), and regimens providing for simultaneous action of both LH and FSH during final oocyte maturation may have beneficial effects on IVF outcomes. Because of the difficulty in improving IVF outcomes in poor responders, the studies on GH are of particular interest. As pointed out in this review, the apparent beneficial effects of GH on oocyte competence may also apply to older women or to normal responders with reduced embryo quality. A much more difficult question is whether and how much ovarian stimulation impacts on oocyte competence. Paradoxically it seems that there are not demonstrated differences between the stimulated and the natural unstimulated cycle, whereas studies in laboratory animals and IVF patients have shown deleterious effects of higher compared with lower doses of gonadotropins. Recent studies suggest that the use of high doses of gonadotropins as an independent factor correlates negatively with the probability of live birth, whereas a high ovarian response per se is associated with better cumulative pregnancy rates, owing to the availability of more euploid and good-quality embryos. Although adjunctive use of androgens has not been discussed here, it is briefly covered in the first review of this series.

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Role of carbohydrate of human chorionic gonadotropin in the mechanism of hormone action

Cited by 240 publications

References 20 publications

Expression of Human Thyrotropin in Cell Lines with Different Glycosylation Patterns Combined with Mutagenesis of Specific Glycosylation Sites

Expression of Human Thyrotropin in Cell Lines with Different Glycosylation Patterns Combined with Mutagenesis of Specific Glycosylation Sites

Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone–receptor interactions

Regimen of ovarian stimulation affects oocyte and therefore embryo quality

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