Metabolism of gonadotropins: comparisons of the primary structures of the human pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate universality of core production.
The gonadotropins are a family of closely related heterodimeric glycoprotein hormones homologous in structure to disulfide-knot growth factors. Metabolic proteolytic processing in vivo of this disulfide cross-linked region results in urinary excretion of a residual highly stable core structure. The primary structure of the pituitary form of the hLH beta core was reported earlier, but it has proved difficult to isolate the urinary core, although antibodies to the pituitary core demonstrated its presence. By conventional and immunoaffinity methods, the urinary core has been isolated and its structure determined by both chemical and mass spectrometric methods. The urinary hLH beta core is the same as the pituitary-extracted hLH beta core, beta 6-40 disulfide bridged to beta 55-93, except that the pituitary core is more heterogeneous containing also beta 49-93. These findings imply a dual origin of urinary cores, both directly from a secreting tissue and by kidney processing of circulating hormone. We also found that pregnant chimpanzees excrete a CG beta core with a primary structure identical to that of the human CG beta core of pregnancy. In conclusion, gonadotropin core generation and urinary excretion of nearly identical gonadotropin metabolites is common among primates. Although possible biological functions of these core fragments remain unproven, they have diagnostic utility because of their stability and abundance.
Birken
S
S
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. sb18@columbia.edu
Gawinowicz
M A
MA
Maydelman
Y
Y
Milgrom
Y
Y
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis* / Q000235:genetics; D000818:Animals; D006063:Chorionic Gonadotropin / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit / Q000652:urine; D006801:Humans; D007120:Immunochemistry; D007986:Luteinizing Hormone / Q000652:urine; D008969:Molecular Sequence Data; D008970:Molecular Weight; D002679:Pan troglodytes / Q000378:metabolism*; D010902:Pituitary Gland / Q000737:chemistry; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013048:Specimen Handling
D000596:Amino Acids; D006063:Chorionic Gonadotropin; D015292:Glycoprotein Hormones, alpha Subunit; D007986:Luteinizing Hormone