Sulfonate and sialic acid groups on human glycoprotein hormones - physiological and clinical significance. Together with Karin Eriksson, BSci.
Both sulfonation and sialylation have major functions in modulating the biological activities of the pituitary glycoprotein hormones: FSH, LH and TSH. The oligosaccharides of these hormones often terminate with sialic acid or SO3--4GalNAc. Increased number of sialic acid increases the half-life in the circulation and can reduce the receptor affinity at the target organ. Molecules with increased number of sulfonated GalNAc disappear more rapidly from the circulation due to binding to a specific SO3--4GalNAc-receptor in the liver. Reported studies have hitherto been restricted to hormones purified from large pools of human pituitaries.
We have developed a method for estimation of the number of sialic acid and sulfonate groups per FSH, LH and TSH molecule in individual serum samples (about 1 mL). The method is based upon neuraminidase treatment, electrophoresis and immunofluorometric hormone assays.
Our preliminary results indicate that all serum samples contain a large number of isoforms with different numbers of sulfonate and sialic acid groups. The distribution of molecules with different numbers of SO3--4GalNAc is determined for each sample. There is a large variation between individuals and there are considerable changes during life from birth to old age.
There are also large changes during the menstrual cycle and at menopause. The effects of oestradiol and a progestogen on sulfonation and sialylation of FSH and LH are investigated. Furthermore, the changes on the FSH and LH isoforms in blood after administration of GnRH and an GnRH-antagonist are studied. The effect of thyroxin on the number of sulfonate and sialic acid groups on serum TSH is also investigated. The clinical significance of sulfonation and sialylation of these glycoprotein hormones is at present studied in women with polycystic ovarian syndrome (PCOS), in patients with hypothyroidism, and in pre-term born girls.