Human FSH isoforms: carbohydrate complexity as determinant of in-vitro bioactivity.
Differences in sialic acid content of the hormone have been considered the main determinant of FSH polymorphism. The aim of the present study was to investigate the effect of variations in the oligosaccharide structure of the intrapituitary human FSH (hFSH) glycosylation variants on their intrinsic biological activity. FSH charge isoforms obtained after chromatofocusing were further separated by lectin affinity chromatography [Concanavalin A (ConA), Wheat germ agglutinin (WGA), Lentil lectin (LcH)]. Isolated isoforms were separately tested for in-vitro bioactivity in a rat Sertoli cell aromatization bioassay. Our results show that: (1) FSH microheterogeneity is due not only to variations in the sialic acid content of the hormone but also to differences in the internal structure of the carbohydrate chains, and (2) variations in the sialic acid content as well as differences in the complexity of the glycans determine the full biological expression of FSH glycosylation variants.
Creus
S
S
Centro de Investigaciones Endocrinológicas. Hospital General de Niños "R. Gutiérrez", Gallo 1330. C.P. 1425, Buenos Aires, Argentina.
Chaia
Z
Z
Pellizzari
E H
EH
Cigorraga
S B
SB
Ulloa-Aguirre
A
A
Campo
S
S
D000818:Animals; D002240:Carbohydrate Sequence; D002846:Chromatography, Affinity; D003208:Concanavalin A; D005640:Follicle Stimulating Hormone / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D014644:Genetic Variation; D006801:Humans; D037102:Lectins; D019158:N-Acetylneuraminic Acid; D009844:Oligosaccharides / Q000737:chemistry; D010902:Pituitary Gland / Q000737:chemistry; D037121:Plant Lectins; D011110:Polymorphism, Genetic; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D014909:Wheat Germ Agglutinins
D037102:Lectins; D009844:Oligosaccharides; D037121:Plant Lectins; D020033:Protein Isoforms; D014909:Wheat Germ Agglutinins; C033619:lentil lectin; D003208:Concanavalin A; D005640:Follicle Stimulating Hormone; D019158:N-Acetylneuraminic Acid