The common genetic variant of luteinizing hormone has a longer serum half-life than the wild type in heterozygous women

Abstract

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 sulfonatedN-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-typeLH(148 vs. 108 min; P < 0.001). VariantLHhadmoresialic acid residues per molecule thanwildtype(3.6 vs. 2.4;P < 0.05), whereasthenumberofsulfonatedresidueswassimilar (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: VariantLHremains longer in circulation than wild type duringGnRHreceptor blockade in heterozygous women, in accord with its higher content of sialic acid. Copyright © 2010 by The Endocrine Society.