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

EMBO J. 1991 Jul;10(7):1885-90.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cells, Cultured
  • Chimera
  • Humans
  • Leucine / genetics*
  • Molecular Sequence Data
  • Protein Conformation
  • Receptors, FSH / chemistry
  • Receptors, FSH / genetics
  • Receptors, Gonadotropin / chemistry
  • Receptors, Gonadotropin / genetics*
  • Receptors, LH / chemistry
  • Receptors, LH / genetics*
  • Repetitive Sequences, Nucleic Acid*
  • Signal Transduction

Substances

  • Receptors, FSH
  • Receptors, Gonadotropin
  • Receptors, LH
  • Leucine