Amino-terminal leucine-rich repeats in gonadotropin receptors determine hormone selectivity.

Abstract

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.