Is there any physiological role for gonadotrophin oligosaccharide heterogeneity in humans? I. Gondatrophins are synthesized and released in multiple molecular forms. A matter of fact.
Carbohydrates attached to the protein core of all glycoprotein hormones play an essential role in the function of the molecule, influencing a number of intracellular and extracellular processes. As with other members of the glycoprotein hormone family, pituitary gonadotrophins are not produced as single 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 isoforms 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 menstrual cycle) promote the formation and secretion of variants with relatively low sialic acid and/or sulphate content, whereas physiological deficiency of this sex steroid (as in the postmenopause) favours the production of highly sialylated, long-lived gonadotrophin variants. When tested individually, less sialylated isoforms exhibit higher receptor-binding and in-vitro biological activity but shorter plasma half-life than their more sialylated counterparts. Both the hormonal regulation and the functional differences among the naturally occurring isoforms strongly suggest that gonadotrophin heterogeneity represents a distinctly different mechanism through which the pituitary gland may regulate the intensity and duration of the gonadotrophic stimulus. Nevertheless, whereas the existence of the alternatively glycosylated variants of gonadotrophins in both the pituitary and in serum is currently without doubt, the physiological role of this phenomenon is still a controversial issue and a matter of debate.
Ulloa-Aguirre
A
A
Research Unit in Reproductive Medicine and Developmental Biology, Instituto Mexicano del Seguro Social, Mexico City, Mexico. aulloaa@buzon.main.conacyt.mx
Timossi
C
C
Méndez
J P
JP
D000818:Animals; D005260:Female; D018740:Genetic Heterogeneity; D006062:Gonadotropins / Q000097:blood / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism*; D011110:Polymorphism, Genetic; D020033:Protein Isoforms
D006062:Gonadotropins; D009844:Oligosaccharides; D020033:Protein Isoforms