Effects of 17β-oestradiol and norethisterone acetate on sulfonation and sialylation of gonadotrophins in post-menopausal women

BACKGROUND: The number of terminal sialic acid and sulfonated N-acetylgalactosamine (SO(3)-GalNAc) on gonadotrophins in serum varies during the menstrual cycle and changes at menopause, suggesting that gonadal steroids modify their oligosaccharide synthesis. Our objective was to determine the effects of 17β-oestradiol (E(2)) and a progestogen, norethisterone acetate (NETA), on the sulfonation and sialylation of gonadotrophins in post-menopausal women. METHODS: Serum samples were obtained from eight post-menopausal women treated with 20 mg E(2) implants every 6 months, from four women who in addition were treated daily with 5 mg NETA orally for a 2-week period, and from four women who got this NETA treatment during a 4-week period. Sera from 11 non-treated post-menopausal women served as a reference group. The gonadotrophin serum concentrations, the number of SO(3)-GalNAc and sialic acid residues per serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) molecule, and the distributions of molecules with 0-1-2-3-4 sulfonated residues were measured. RESULTS: The E(2)-treated post-menopausal women had considerably less (P < 0.001) sialic acid and slightly more (P < 0.01) SO(3)-GalNAc per serum LH and FSH molecule than the non-treated. Two weeks of NETA treatment increased the sulfonation of LH (P < 0.01) and FSH (P < 0.05) concomitantly with decreased (P < 0.05) sialylation of LH. CONCLUSION: The primary effect of E(2) treatment was a decrease in sialylation and, due to competition for the same substrate, a secondary and consequentially minor increase in sulfonation of LH and FSH. The primary effect of the NETA therapy was an increase in the sulfonation of LH and FSH concomitantly with secondary and consequentially decreases in sialylation of LH.