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

Figures & data

Table I.  Sialic acid and sulfonated GalNAc residues per LH and FSH molecule in serum and frequency of isoforms with zero to four sulfonated GalNAc residues. Four groups of post-menopausal women: non-treated, treated with 20 mg E₂ implant, and, in addition to E₂, with 2 and 4 weeks of oral therapy with 5 mg NETA daily.

Group	Non-treated	E2-implant	E2+2wNETA	E2+4wNETA
Number of women	11	8	4	4
LH; mean ± SEM
Serum level (IU/L)	24.4 ± 1.80	10.2 ± 2.21^b	3.08 ± 0.56^a	1.48 ± 0.48^a,d
Sialic acid residues	2.64 ± 0.04	2.14 ± 0.04^c	1.86 ± 0.04^a	1.57 ± 0.06^a,d
Sulfonated GalNAc	0.99 ± 0.04	1.15 ± 0.03^b	1.64 ± 0.03^b	1.80 ± 0.03^a,d
Ratio Sial./Sulf.	2.70 ± 0.11	1.87 ± 0.07^c	1.14 ± 0.04^b	0.87 ± 0.04^a,d
Negatively charged residues	3.64 ± 0.03	3.29 ± 0.03^c	3.50 ± 0.02^b	3.37 ± 0.05
Zero SO3-GalNAc (%)	30.7 ± 2.44	28.1 ± 0.90	14.2 ± 2.62^b	6.04 ± 2.43^d
One SO3-GalNAc (%)	46.9 ± 3.54	40.3 ± 2.08	30.8 ± 2.91	28.6 ± 2.96
Two SO3-GalNAc (%)	15.9 ± 2.57	21.5 ± 2.40	37.5 ± 2.26^b	45.5 ± 11.2^d
Three SO3-GalNAc (%)	5.80 ± 1.40	8.68 ± 2.00	14.4 ± 1.65	18.9 ± 6.77
Four SO3-GalNAc (%)	0.79 ± 0.36	1.42 ± 0.65	3.82 ± 1.15	0.91 ± 0.77
Two to four SO3-GalNAc (%)	22.4 ± 1.92	31.6 ± 1.89	55.7 ± 1.51^b	65.3 ± 4.58^a,d
FSH; mean ± SEM
Serum level (IU/L)	56.5 ± 4.01	10.4 ± 2.63^c	4.20 ± 1.31	2.21 ± 0.41^a,d
Sialic acid residues	7.55 ± 0.03	6.53 ± 0.11^c	6.68 ± 0.07	6.17 ± 0.10^a
Sulfonated GalNAc	0.22 ± 0.03	0.39 ± 0.03^b	0.58 ± 0.04^a	0.80 ± 2.73^a,d
Ratio Sial./Sulf.	44.5 ± 9.98	17.4 ± 1.49^c	11.7 ± 1.0	7.71 ± 0.39^a,d
Negatively charged residues	7.55 ± 0.03	6.92 ± 0.12^c	7.26 ± 0.05^a	7.00 ± 0.06^a
Zero SO3-GalNAc (%)	86.6 ± 2.08	74.1 ± 2.34^b	63.6 ± 2.90^a	48.6 ± 2.46^a,d
One SO3-GalNAc (%)	4.93 ± 1.17	13.2 ± 2.49^b	15.1 ± 1.39	24.0 ± 3.31
Two SO3-GalNAc (%)	8.07 ± 1.03	12.1 ± 1.32^a	20.8 ± 2.11^b	26.3 ± 1.15^a,d
Two to four SO3-GalNAc (%)	8.45 ± 1.00	12.8 ± 1.14^a	21.3 ± 1.63^b	27.4 ± 1.62^a,d

Statistical comparisons with non-parametric Mann-Whitney test.

^aP < 0.05 versus preceding group.

^bP < 0.01 versus preceding group.

^cP < 0.001 versus preceding group.

^dP < 0.01 versus E₂-implant group.

Figure 1.  Relationship between LH concentration and changes in the number of sialic acid (open star) and sulfonated (filled circle) residues and negatively charged residues (filled square) on the oligosaccharides per LH molecule after 2 and 4 weeks of NETA therapy in two E₂-implant-treated post-menopausal women. The average numbers of sialic acid (SA^-) and sulfonated (SO₃^-) residues per serum LH molecule at the start of NETA treatment are given (w = weeks).

Figure 2.  Relationship between FSH concentration and changes in the number of sialic acid (open star) and sulfonated (filled circle) residues and negatively charged residues (filled square) on the oligosaccharides per FSH molecule after 2 and 4 weeks of NETA therapy in two E₂-implant-treated post-menopausal women. The average numbers of sialic acid (SA^-) and sulfonated (SO₃^-) residues per serum FSH molecule at the start of NETA treatment are given (w = weeks).

Figure 3.  Mean ± SEM of average number of sialic acid (lower panels) and sulfonated GalNAc (upper panels) residues per serum LH (left panels) and FSH (right panels) molecule in four groups of post-menopausal women. NETA was given to E₂-implant-treated women, and sera were taken at the start (E₂-implant) and after 2 (E₂+2wNETA) and 4 (E₂+4wNETA) weeks of treatment (non-treated = a reference group of non-treated post-menopausal women). Statistical comparison with preceding group. *P < 0.05; **P < 0.01; ***P < 0.001. Figures in parentheses indicate number of women in each group.

Figure 4.  Relationship between serum LH (upper panel) and FSH (lower panel) concentration and number of sialic acid (open star) and sulfonated GalNAc (filled circle) residues per molecule in four groups of post-menopausal women. NETA was given to E₂-implant-treated women, and sera were taken at the start (E₂-implant) and after 2 (E₂+2wNETA) and 4 (E₂+4wNETA) weeks of treatment (non-treated = a reference group of nine non-treated post-menopausal women). Significance of difference in number of residues/concentration is indicated. *P < 0.05; **P < 0.01; ***P < 0.001; ns = not significant. Figures in parentheses indicate number of women in each group.