Structures of N-glycosidic carbohydrate units of human chorionic gonadotropin.

Kessler, Michael J.; Reddy, M. Siva Pratap; Shah, Ramesh H.; Bahl, Om P.

doi:10.1016/s0021-9258(18)36031-9

Cited by 231 publications

(9 citation statements)

References 26 publications

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“…The role of the surge is to induce the final stages of oocyte maturation (most importantly, resumption of meiosis) and to induce ovulation. As a routine, hCG, a biologic homolog to LH, has been used in the IVF setting as a surrogate for the LH surge to trigger oocyte maturation (98).…”

Section: The Lack Of An Fsh Surge Has Been An Unphysiologic Aspect Of Most Ivf Cycles: Ways To Restore Fsh Exposure To the Oocyte At Thismentioning

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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Section: The Lack Of An Fsh Surge Has Been An Unphysiologic Aspect Of Most Ivf Cycles: Ways To Restore Fsh Exposure To the Oocyte At Thismentioning

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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“…These hormones are heterodimers consisting of an ct subunit that is common among the four hormones, and a 13 subunit that gives each its unique biological activity (5,36,53). The hCGa subunit contains two asparagine (Asn)-linked oligosaccharide chains (13,23), whereas the hCG13 subunit contains two Asn-linked and four serine O-linked carbohydrate units (3,22,24).…”

mentioning

confidence: 99%

The role of the asparagine-linked oligosaccharides of the alpha subunit in the secretion and assembly of human chorionic gonadotrophin.

Matzuk

Boime

1988

The Journal of Cell Biology

204

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Abstract. Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common ct subunit but differ in their hormone-specific 13 subunit. Site-directed mutagenesis of the two asparagine-linked glycosylation sites of hCGct was used to study the function of the individual oligosaccharide chains in secretion and subunit assembly. Expression vectors for the ~t genes (wild-type and mutant) and the hCG[3 gene were constructed and transfected into Chinese hamster ovary cells. Loss of the oligosaccharide at position 78 causes the mutant subunit to be degraded quickly and <20% is secreted. However, the presence of hCG[3 stabilizes this mutant and allows ~45% of the subunit in the form of a dimer to exit the cell. Absence of carbohydrate at asparagine 52 does not perturb the stability or transport of the ct subunit but does affect dimer secretion; under conditions where this mutant or hCGI3 was in excess, <30% is secreted in the form of a dimer. Mutagenesis of both glycosylation sites affects monomer and dimer secretion but at levels intermediate between the single-site mutants. We conclude that there are site-specific functions of the hCGct asparaginelinked oligosaccharides with respect to the stability and assembly of hCG. HUMAN chorionic gonadotropin (hCG) ~ is a member of the glycoprotein hormone family which includes lutropin, follitropin, and thyrotropin. These hormones are heterodimers consisting of an ct subunit that is common among the four hormones, and a 13 subunit that gives each its unique biological activity (5,36,53). The hCGa subunit contains two asparagine (Asn)-linked oligosaccharide chains (13, 23), whereas the hCG13 subunit contains two Asn-linked and four serine O-linked carbohydrate units (3,22,24).Several studies have addressed the role of the Asn-linked oligosaccharide chains on the gonadotropins. Chemical or enzymatic methods have been used to remove all or part of the oligosaccharide chains to obtain a better understanding of carbohydrate function. While desialylation of hCG causes it to be rapidly cleared via the hepatic route (32), its effects on biological activity in vitro are not clear (1,33,51). Removal of carbohydrate internal to sialic acid or complete deglycosylation converts hCG into an antagonist; it binds more tightly to its receptor, but shows decreased biological activity in vitro (6,21,25,33). Although the role of the oligosaccharide side-chains in folding and assembly of the hCG subunits in vivo is unknown, it has been postulated that 1. Abbreviations used in this paper: Asn, asparagine; CHO. Chinese hamster ovary; Endo F, Endoglycosidase F; Endo H, Endoglycosidase H; hCG, human chorionic gonadotropin; Thr, threonine. these oligosaccharides are important for correct disulfide bond formation (48). Combination of hCG subunits apparently occurs when the oligosaccharides are removed chemically (21, 25) or enzymatically (16). However, one problem with these methods is that incompletely deglycosylated derivatives are generated; in additio...

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“…Despite these similarities, human LH and CG bear N-linked oligosaccharides that are structurally distinct (reviewed by Green et al, 1986). The oligosaccharides of LH contain terminal N-acetylgalactosamine residues that are sulfated (Green et al, 1986) while those of CG terminate with galactose and sialic acid (Endo et al, 1979;Kessler et al, 1979;Mizuochi et al, 1979). Understanding the processing of LH and CG oligosaccharides is important in view of their role in the bioactivity of the hormones.…”

mentioning

confidence: 99%

Gonadotropin beta subunits determine the rate of assembly and the oligosaccharide processing of hormone dimer in transfected cells.

Corless

Matzuk

Ramabhadran

et al. 1987

The Journal of Cell Biology

113

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Abstract. The glycoprotein hormones lutropin (LH) and chorionic gonadotropin (CG) share a common structure consisting of an identical st subunit noncovalently linked to a hormone-specific 13 subunit. While LH is produced in the anterior pituitary, CG is synthesized in placenta. To compare the assembly, processing, and secretion of human LH and CG in the same cell type, we have expressed their subunits, individually and together, in mouse C-127 mammary tumor cells. Analysis of transfected clones revealed an unexpected difference in the secretion of individually expressed subunits. Whereas st and CG13 subunits were rapidly and quantitatively secreted, only 10% of newly synthesized LH13 subunit reached the medium. The remaining subunit was found in an intracellular, endoglycosidase H (endo H)-sensitive pool that had a turnover rate of ~8 h. Coexpression with st subunit resulted in "rescue" of LH13 subunit by formation of LH dimer, which was efficiently secreted. However, combination of LH13 with st was slow, with an overall efficiency of only 50% despite the presence of excess st. In contrast, CG13 was rapidly assembled with the st subunit after synthesis. The two 13 subunits also differed in their influence on the N-linked oligosaccharide processing of combined st. The oligosaccharides of LH dimer were endo H resistant, while those of CG dimer remained partially endo H sensitive. Thus, despite a high degree of homology between LH13 and CG13, the two subunits differ in their secretion as free subunits, their rate of assembly with st subunit, and in their effect on the N-linked oligosaccharide processing of combined st. UTROPIN (LH), t and chorionic gonadotropin (CG) are members of the glycoprotein hormone family that also includes follitropin (FSH) and thyrotropin. Each of these hormones is composed of two noncovalently linked subunits, et and 13. Within a species, the ¢t subunits of the hormones are identical in amino acid sequence, while the unique 13 subunits determine biological specificity (Pierce and Parsons, 1981;Sairam, 1983). LH, which is made in the pituitary, and CG, a product of the placenta, are the most closely related among the hormones in both structure and function. Amino acid homology of human LH13 and CG13 subunits exceeds 80%, including full conservation of cysteine residues (Shome and Parlow, 1973;Carlsen et al., 1973;Morgan et al., 1975;Keutmann et al., 1979). This close homology allows the 13 subunits, in concert with st subunit, to bind the same gonadal receptors (Rajaniemi and VanhaPerttula, 1972;Haour and Saxena, 1974). Full biological ac-1. Abbreviations used in this paper: BPV, bovine papilloma virus; CG, chorionic gonadotropin; endo F, endoglycosidase F; endo H, endoglycosidase H; ER, endoplasmic reticulum; FSH, follitropin; LH, lutropin; MT, mouse metallothionein-I. tivity of LH and CG is dependent on the N-linked oligosaccharides present on both the ~ and 13 subunits (Moyle et al., 1975;Sairam, 1983).Despite these similarities, human LH and CG bear N-linked oligosaccharides that ar...

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Structures of N-glycosidic carbohydrate units of human chorionic gonadotropin.

Cited by 231 publications

References 26 publications

Regimen of ovarian stimulation affects oocyte and therefore embryo quality

Regimen of ovarian stimulation affects oocyte and therefore embryo quality

The role of the asparagine-linked oligosaccharides of the alpha subunit in the secretion and assembly of human chorionic gonadotrophin.

Gonadotropin beta subunits determine the rate of assembly and the oligosaccharide processing of hormone dimer in transfected cells.

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