Serum half-life of pituitary gonadotropins is decreased by sulfonation and increased by sialylation in women.
BACKGROUND
The gonadotropins are secreted from the human pituitary as spectra of isoforms with different degrees of sulfonation and sialylation of the oligosaccharides, modifications suspected to determine their half-lives in the circulation.


OBJECTIVE
Our objectives were to determine the isoform composition of the serum gonadotropins during GnRH receptor blockade, and to estimate the half-lives in circulation of isoforms with 0-1-2-3 sulfonated N-acetylgalactosamine (SO(3)-GalNAc) residues.


METHODS
Serum samples were collected in seven healthy women before and up to 20 h after administration of the NAL-GLU GnRH antagonist.


METHODS
The number of sialic acid and SO(3)-GalNAc residues per LH and FSH molecule and the distribution of molecules with 0-1-2-3 sulfonated residues were measured. The half-lives were estimated by monoexponential decay.


RESULTS
More sialylated and less sulfonated gonadotropin isoforms remain longer in circulation during GnRH receptor blockade. LH isoforms with two and three sulfonated residues per molecule had shorter half-lives compared with those with zero and one (109 and 80 vs. 196 and 188 min; P < 0.01). FSH isoforms with one and two sulfonated residues had shorter half-lives than those with zero (485 and 358 vs. 988 min; P < 0.01).


CONCLUSIONS
The decline in LH and FSH during GnRH receptor blockade is associated with a decrease in sulfonated and increase in sialylated residues. The rapid disappearance of LH isoforms with two and three SO(3)-GalNAc residues suggests their removal by hepatic SO(3)-GalNAc-receptors similar to those in rodents. Episodical secretion of spectra of isoforms with different half-lives is expected to lead to continuous changes in gonadotropin isoform compositions in blood.
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
D000116:Acetylgalactosamine / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006207:Half-Life; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D020033:Protein Isoforms; D013451:Sulfonic Acids / Q000378:metabolism*
D020033:Protein Isoforms; D013451:Sulfonic Acids; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D019158:N-Acetylneuraminic Acid; D000116:Acetylgalactosamine