Human chorionic gonadotropin with C-elongated alpha-subunit retains full receptor binding and partial agonist activity.
OBJECTIVE
To test whether extension of the C-terminus of human chorionic gonadotropin (hCG) alpha-subunit (halpha) alters the bioactivity of the recombined alphabeta heterodimer.


METHODS
The stop codon of halpha was mutated to produce a 24 amino acid extension.


METHODS
The extended halpha (alpha(+24)) was co-expressed with hCGbeta in COS-7 cells and the receptor binding and in vivo bioactivity of the secreted hormone was compared with its wild-type counterpart.


RESULTS
This extension did not impair the binding of hCG to rat LH/CG receptors and provoked a sixfold reduction in its stimulatory activity of testosterone secretion in rat Leydig cells.


CONCLUSIONS
The extension of alpha by itself does not lead to inhibition of the alphabeta heterodimer to LH receptors but the structure of the extension appears to play an important role. It is thus possible that one-chain hCG chimeras with the beta N-terminus fused to the alpha C-terminus might be active.
Marichatou
H
H
Laboratoire de Physiologie de la Reproduction des Mammifères Domestiques, INRA-CNRS URA1291 37380 Nouzilly, France.
Martinat
N
N
Guillou
F
F
Combarnous
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D003062:Codon / Q000235:genetics; D006801:Humans; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000502:physiology*; D051381:Rats; D011974:Receptors, LH / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000378:metabolism
D006063:Chorionic Gonadotropin; D003062:Codon; D011974:Receptors, LH; D011994:Recombinant Proteins; D013739:Testosterone; D007986:Luteinizing Hormone