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The common genetic variant of luteinizing hormone has a longer serum half-life than the wild type in heterozygous women
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
2010 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 1, 383-389 p.Article in journal (Refereed) Published
Abstract [en]

CONTEXT: The common genetic variant of human LH has two mutations and an extra N-linked oligosaccharide chain, a modification expected to affect the half-life in the circulation. OBJECTIVES: Our objectives were to determine the half-lives of variant and wild-type forms of LH during GnRH receptor blockade in heterozygous women and to determine the time-related changes in isoform composition. DESIGN AND PARTICIPANTS: Serum samples were obtained from three healthy women heterozygous for variant LH before and up to 20 h after administration of the NAL-GLU GnRH antagonist. MAIN OUTCOME MEASURES: The half-lives were estimated by monoexponential decay. The number of sialic acid and sulfonated N-acetylgalactosamine residues per wild-type and variant LH molecule and the distribution of molecules with zero, one, two, or three sulfonated residues were measured. RESULTS: The variant LH had a half-life that was approximately 40% longer than the corresponding forms of wild-type LH (148 vs. 108 min; P < 0.001). Variant LH had more sialic acid residues per molecule than wild type (3.6 vs. 2.4; P < 0.05), whereas the number of sulfonated residues was similar (1.0 vs. 0.98). The decline in the variant LH during GnRH receptor blockade was associated with a decrease in sulfonated and an increase in sialic acid residues similar to that for in wild-type LH. Isoforms of either variant or wild-type LH with two to three sulfonate groups per molecule had the shortest half-life. CONCLUSION: Variant LH remains longer in circulation than wild type during GnRH receptor blockade in heterozygous women, in accord with its higher content of sialic acid.

Place, publisher, year, edition, pages
2010. Vol. 95, no 1, 383-389 p.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-120820DOI: 10.1210/jc.2009-1679ISI: 000273391300055PubMedID: 19890021OAI: oai:DiVA.org:uu-120820DiVA: diva2:303995
Available from: 2010-03-16 Created: 2010-03-16 Last updated: 2017-12-12Bibliographically approved

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