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Equine lutropin and chorionic gonadotropin bear oligosaccharides terminating with SO4-4-GalNAc and Sia alpha 2,3Gal, respectively.
Abstract: Equine chorionic gonadotropin (eCG) and lutropin (eLH) are heterodimeric glycoprotein hormones which are synthesized in the placenta and pituitary, respectively. The beta subunits of eCG and eLH, like their alpha subunits, arise from a single gene and have identical amino acid sequences. In contrast, the beta subunits of CG and LH in primates arise from different genes and differ in sequence. We have examined the structures of the Asn-linked oligosaccharides on eCG and eLH. eCG bears di- and tri-branched Asn-linked oligosaccharides terminating with Sia alpha 2,3 or 6Gal beta 1,4GlcNAc. In contrast, > 72% of the Asn-linked oligosaccharides on eLH have 1 or 2 branches terminating with the sequence SO4-4-GalNAc beta 1,4GlcNAc. The nonsulfated oligosaccharides on eLH are neutral (6% of the total) or have branches terminating with sialic acid-Gal (22% of the total). Since the alpha and beta subunits of eCG and eLH both contain the tripeptide motif, Pro-Xaa-Arg/Lys, recognized by the glycoprotein hormone-specific GalNAc-transferase found in pituitary, expression of the GalNAc- and sulfotransferases must differ in the placenta and pituitary. eLH, but not eCG, is bound by the hepatic endothelial cell receptor specific for the sequence SO4-4-GalNAc beta 1,4GlcNAc. As a result, eLH is removed from the circulation 5.7-fold more rapidly than eCG and is selectively localized to the liver. Since the major structural difference between eCG and eLH is in the terminal glycosylation of their Asn-linked oligosaccharides and this has a major impact on circulatory half-life, it is likely that the difference in circulatory half-life defines the functional difference between eCG and eLH.
Publication Date: 1993-01-15 PubMed ID: 8419356 The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Comparative Study
- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research article focuses on understanding the structures of the Asn-linked oligosaccharides in equine lutropin (eLH) and chorionic gonadotropin (eCG) hormones, synthesized in the pituitary and placenta respectively. It argues that the structural differences, particularly in terminal glycosylation of the oligosaccharides, significantly influence these hormones’ circulatory half-life, potentially defining their functional disparities.
Understanding eCG and eLH Characteristics
- The paper starts by describing eCG and eLH as heterodimeric glycoprotein hormones. They are generated respectively in the placenta and pituitary, presumably because these parts have suitable environments for their production. Despite their unique production sites, both hormones’ alpha and beta subunits arise from a single gene and have identical amino acid sequences.
Uncovering the Oligosaccharides’ Structures
- Further into the research, investigators examined the structures of the Asn-linked oligosaccharides present in eCG and eLH.
- eCG features di- and tri-branched Asn-linked oligosaccharides that end with Sia alpha 2,3, or 6Gal beta 1,4GlcNAc.
- Almost 72% Asn-linked oligosaccharides on eLH, on the other hand, display one or two branches ending with the sequence SO4-4-GalNAc beta 1,4GlcNAc. Other nonsulfated oligosaccharides on eLH are either neutral (comprising 6% of the total) or their branches end with sialic acid-Gal (making up 22% of the total).
Implications of Differences in Expressions of GalNAc- and Sulfotransferases
- Since both alpha and beta subunits of eCG and eLH contain the tripeptide motif, Pro-Xaa-Arg/Lys (which is recognized by GalNAc-transferase, a hormone-specific enzyme in the pituitary), distinct expression of GalNAc- and sulfotransferases in the placenta and pituitary must be the source of key differences between eCG and eLH.
- eLH, unlike eCG, is bound by a receptor, specific to the sequence SO4-4-GalNAc beta 1,4GlcNAc, found on liver endothelial cells. As such, eLH gets removed from circulation 5.7 times faster than eCG and is selectively localized to the liver.
Role of Terminal Glycosylation in Functional Differences
- Ultimately, since the major structural distinction between eCG and eLH lies in the terminal glycosylation of their Asn-linked oligosaccharides, which significantly influences their time in circulation, the researchers postulate that the difference in circulatory half-life could be the determining factor of their functional roles.
Cite This Article
APA
Smith PL, Bousfield GR, Kumar S, Fiete D, Baenziger JU.
(1993).
Equine lutropin and chorionic gonadotropin bear oligosaccharides terminating with SO4-4-GalNAc and Sia alpha 2,3Gal, respectively.
J Biol Chem, 268(2), 795-802.
Publication
Researcher Affiliations
- Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
MeSH Terms
- Animals
- Carbohydrate Conformation
- Carbohydrate Sequence
- Chorionic Gonadotropin / chemistry
- Chorionic Gonadotropin / metabolism
- Chorionic Gonadotropin / pharmacokinetics
- Chromatography, Affinity
- Chromatography, High Pressure Liquid
- Chromatography, Ion Exchange
- Endothelium / metabolism
- Female
- Horses
- Humans
- Kidney / metabolism
- Kinetics
- Liver / metabolism
- Luteinizing Hormone / chemistry
- Luteinizing Hormone / metabolism
- Luteinizing Hormone / pharmacokinetics
- Macromolecular Substances
- Metabolic Clearance Rate
- Molecular Sequence Data
- Oligosaccharides / analysis
- Oligosaccharides / chemistry
- Oligosaccharides / isolation & purification
- Pituitary Gland / metabolism
- Placenta / metabolism
- Pregnancy
- Rats
Grant Funding
- R01-DK41738 / NIDDK NIH HHS
Citations
This article has been cited 15 times.- Byambaragchaa M, Park A, Gil SJ, Lee HW, Ko YJ, Choi SH, Kang MH, Min KS. Luteinizing hormone-like and follicle-stimulating hormone-like activities of equine chorionic gonadotropin β-subunit mutants in cells expressing rat luteinizing hormone/chorionic gonadotropin receptor and rat follicle-stimulating hormone receptor. Anim Cells Syst (Seoul) 2021;25(3):171-181.
- Min KS, Park JJ, Byambaragchaa M, Kang MH. Characterization of tethered equine chorionic gonadotropin and its deglycosylated mutants by ovulation stimulation in mice. BMC Biotechnol 2019 Aug 13;19(1):60.
- Kara E, Dupuy L, Bouillon C, Casteret S, Maurel MC. Modulation of Gonadotropins Activity by Antibodies. Front Endocrinol (Lausanne) 2019;10:15.
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- Mereness AL, Murphy ZC, Forrestel AC, Butler S, Ko C, Richards JS, Sellix MT. Conditional Deletion of Bmal1 in Ovarian Theca Cells Disrupts Ovulation in Female Mice. Endocrinology 2016 Feb;157(2):913-27.
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- Bedi GS. Asparagine-linked carbohydrate chains of inducible rat parotid proline-rich glycoprotein contain terminal beta-linked N-acetylgalactosamine. Glycoconj J 1997 Dec;14(8):907-16.
- Dharmesh SM, Baenziger JU. Estrogen modulates expression of the glycosyltransferases that synthesize sulfated oligosaccharides on lutropin. Proc Natl Acad Sci U S A 1993 Dec 1;90(23):11127-31.
- Lösle M, Lin CW, Beil-Wagner J, Aebi M, Buch T. Comparison of pregnant mare serum gonadotropin products with surprising differences in protein content. Sci Rep 2025 Feb 25;15(1):6824.
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