[Glycoprotein hormones, glycosylation and biological activity].
Glycoprotein hormones LH, FSH, TSH and hCG are heterodimeric molecules: each contains two subunits, a common alpha and a unique beta subunit. Each subunit bears one or two Asparagine linked carbohydrate moieties which have a biantennary complex-type or hybrid-type structure. Different technical methods as deglycosylation or molecular biology techniques have been used to study the role of carbohydrate residues in hormonal bioactivity. The carbohydrate chains are not directly involved in receptor binding events but their mechanisms of action is not fully understood. Two hypotheses are frequently emphasised: a conformational role or an involvement in the coupling of the receptor-adenylate cyclase system. At the post receptor level carbohydrate chains modulate the bioactivity in two ways: a global regulation following an all-or-none mode and slight one. The removal of the carbohydrate moieties leads to a loss of the in vitro hormonal activity. The results observed are dependent of the deglycosylation techniques and the bioactivity tests used. Hormone's deglycosylation reduces their capacity of production of cAMP and, to a lesser extent, their steroidogenic power. Deglycosylated hormones are antagonists to negative hormones although deglycosylated hCG has some agonist properties in vivo. Microheterogeneity of the glycoprotein hormones is due to slight variations in sialic acid and/or sulfate content. Glycoprotein hormones exist as several isoforms which differ in biological potency. Alkaline isoforms (less sialylated ones) are the most biologically active in vitro but have a short half live in vivo; acid isoforms are less active in vitro but have a longer circulatory half live. The polymorphism of glycoprotein hormones is a highly regulated process.(ABSTRACT TRUNCATED AT 250 WORDS)
Pigny
P
P
Laboratoire d'endocrinologie, USN A, CHU Lille, France.
Berault
A
A
Dewailly
D
D
Boersma
A
A
D006063:Chorionic Gonadotropin / Q000378:metabolism*; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D006031:Glycosylation; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011962:Receptors, FSH / Q000378:metabolism; D011967:Receptors, Gonadotropin / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D011134:Polysaccharides; D011962:Receptors, FSH; D011967:Receptors, Gonadotropin; D011974:Receptors, LH; D011989:Receptors, Thyrotropin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin
Hormones glycoprotéiques, glycosylation et activité biologique.