Amino-terminal leucine-rich repeats in gonadotropin receptors determine hormone selectivity.
Recombinant expression of truncated receptors for luteinizing hormone/chorionic gonadotropin (LH/CG) revealed that the amino-terminal leucine-rich repeats 1-8 of the extracellular receptor domain bind human chorionic gonadotropin (hCG) with an affinity (Kd = 0.72 +/- 0.2 nM) similar to that of the native LH/CG receptor (Kd = 0.48 +/- 0.05 nM). LH/CG receptor leucine-rich repeats 1-8 were used to replace homologous sequences in the closely related receptor for follicle stimulating hormone (FSH). Cells expressing such chimeric LH/CG-FSH receptors bind hCG and show elevated cylic AMP levels when stimulated by hCG but not by recombinant human FSH (rhFSH). Similarly, a chimeric LH/CG receptor in which leucine-rich repeats 1-11 originated from the FSH receptor is activated by rhFSH but not by hCG. For this chimera, no residual [125I] hCG binding was observed in a range of 2 pM to 10 nM. Our results demonstrate that specificity of gonadotropin receptors is determined by a high affinity hormone binding site formed by the amino-terminal leucine-rich receptor repeats.
Braun
T
T
Laboratory of Molecular Neuroendocrinology, University of Heidelberg, FRG.
Schofield
P R
PR
Sprengel
R
R
D001483:Base Sequence; D002478:Cells, Cultured; D002678:Chimera; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011962:Receptors, FSH / Q000737:chemistry / Q000235:genetics; D011967:Receptors, Gonadotropin / Q000737:chemistry / Q000235:genetics*; D011974:Receptors, LH / Q000737:chemistry / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction
D011962:Receptors, FSH; D011967:Receptors, Gonadotropin; D011974:Receptors, LH; D007930:Leucine