Is there any physiological role for gonadotrophin oligosaccharide heterogeneity in humans? I. Gonadotrophins are synthesized and released in multiplemolecular forms. A matter of fact

Carbohydrates attached to the protein core of all glycoprotein hormones pla y an essential role in the function of the molecule, influencing a number o f intracellular and extracellular processes. As with other members of the g lycoprotein hormone family, pituitary gonadotrophins are not produced as si ngle or unique molecules but rather as arrays of isoforms that differ from each other mainly in the structure of their oligosaccharide attachments. In both experimental animals and in humans, the abundance of the different is oforms varies depending on the endocrine status of the donor present at the time of collection of the tissue or sample. Conditions characterized by an oestrogen-enriched hormonal milieu (eg. the preovulatory phase of the mens trual cycle) promote the formation acid secretion of variants with relative ly low sialic acid and/or sulphate content, whereas physiological deficienc y of this sex steroid (as in the postmenopause) favours the production of h ighly sialylated, long-lived gonadotrophin variants. When tested individual ly, less sialylated isoforms exhibit higher receptor-binding and in-vitro b iological activity but shorter plasma half-life than their more sialylated counterparts. Both the hormonal regulation and the functional differences a mong the naturally occurring isoforms strongly suggest that gonadotrophin h eterogeneity represents a distinctly different mechanism through which the pituitary gland may regulate the intensity and duration of the gonadotrophi c stimulus. Nevertheless, whereas the existence of the alternatively glycos ylated variants of gonadotrophins in both the pituitary and in serum is cur rently without doubt, the physiological role of this phenomenon is still a controversial issue and a matter of debate.