[Biological polymorphism and functional domains of pituitary glycoprotein hormones].
The glycoprotein hormones are a family of four proteins: LH, FSH, TSH and CG. These molecules are glycosylated dimers, sharing a common alpha-subunit and differing by their beta-subunit which confers to the hormone its immunological and biological specificity. The biological function of these hormones is mediated through the recognition of specific receptors at the target organ. Although still controversial, it appears that both subunits of the hormone are required to bind to the receptor and induce cAMP release. Furthermore, these hormones exhibit natural variability in their bioactivity and the molecular basis of this process are poorly understood at the moment. Recent data relative to the mapping of glycoprotein hormones, were obtained by site-directed mutagenesis as well as by the use of synthetic peptides. These two approaches allowed to elucidate several linear peptide sequences involved in the biologically active conformation and immunoreactivity of these molecules. Furthermore, these hormones exist in different molecular forms with a variable biological activity and immunological ratio, and this polymorphism is probably due to the glycan moities. The presence of these glycans are necessary for full expression of their biological activity as well as immunoreactivity, and both the biosynthesis and the secretion of these various glycoforms are probably under physiological regulation. We therefore propose that glycosylation may alter the expression of several domains at the surface of the hormone to modulate its plasmatic clearance as well as the action of each individual glycoform at the receptor and this will ultimately control its biological function.
Papandréou
M J
MJ
Laboratoire de Biologie Relationnelle, Faculté de Médecine-Secteur Nord, Marseille.
Darbon
H
H
Ronin
C
C
D006063:Chorionic Gonadotropin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D002874:Chromosome Mapping; D005640:Follicle Stimulating Hormone / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006031:Glycosylation; D006801:Humans; D007986:Luteinizing Hormone / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D010907:Pituitary Hormones / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D013972:Thyrotropin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
D006063:Chorionic Gonadotropin; D010907:Pituitary Hormones; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin
Polymorphisme biologique et domaines fonctionnels des hormones glycoprotéiques hypophysaires.