Sulfonation and sialylation of gonadotropins in women during the menstrual cycle, after menopause, and with polycystic ovarian syndrome and in men

• Context: More basic isoforms of LH and FSH appear in blood at midcycle and more acidic after menopause. The LH isoforms are more basic in women with polycystic ovarian syndrome (PCOS). These charge alterations may reflect differences in the number of two negatively charged residues on the gonadotropins: sialic acid and sulfonated N-acetylgalactosamine, residues that modulate the half-life of the gonadotropins in blood. Objective: The objective of the study was to determine the contributions of sialic acid and sulfonated N-acetylgalactosamine and sialic acid on LH and FSH to the observed alterations in charge. Design/Participants: Serum samples were obtained from 59 young women with regular cycles, nine postmenopausal women, 12 women with PCOS, and 40 young men. Main Outcome Measures: The number of sulfonated N-acetylgalactosamine and sialic acid residues per LH and FSH molecule in serum and the distributions of molecules with 0-1-2-3-4 sulfonated residues were determined by electrophoretic analyses before and after removal of sialic acid. Results: Considerably decreased sulfonation of LH was found at midcycle and in women with PCOS concomitant with slightly increased sialylation. The sulfonation of LH increased in the luteal phase, and the sialylation was highest after menopause for both hormones. The frequencies of sulfonated LH and FSH isoforms were directly related (P < 0.01) to body mass index in women with PCOS. Conclusion: The observed variations in sialic acid and sulfonated residues on serum gonadotropins are suggested to reflect alterations in the isoform composition of the hormones secreted by the pituitary, resulting in modulations of their biological properties, such as half-life in blood.

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