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


OBJECTIVE
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Wide
Leif
L
Department of Clinical Chemistry, University Hospital, SE 751 85 Uppsala, Sweden. leif.wide@medsci.uu.se
Eriksson
Karin
K
Sluss
Patrick M
PM
Hall
Janet E
JE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006207:Half-Life; D006579:Heterozygote; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D050505:Mutant Proteins / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics*; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors; D013997:Time Factors; D055815:Young Adult
C484844:GNRHR protein, human; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D050505:Mutant Proteins; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D019158:N-Acetylneuraminic Acid