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Serum Half-Life of Pituitary Gonadotropins Is Decreased by Sulfonation and Increased by Sialylation in Women

Department of Medical Sciences, Clinical Chemistry (L.W., K.E.), University Hospital, SE 751 85 Uppsala, Sweden; and Reproductive Endocrine Unit, Department of Medicine (P.M.S., J.E.H.), Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Leif Wide, M.D., Ph.D., Department of Clinical Chemistry, University Hospital, SE 751 85 Uppsala, Sweden. E-mail: leif.wide{at}medsci.uu.se.

Context: 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.

Objectives: 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 (SO₃-GalNAc) residues.

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

Main Outcome Measures: The number of sialic acid and SO₃-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 SO₃-GalNAc residues suggests their removal by hepatic SO₃-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.