A receptor binding site identified in the region 81-95 of the β-subunit of human luteinizing hormone (LH) and chorionic gonadotropin (hCG)

Dean E. Morbeck, Patrick C. Roche, Henry T. Keutmann, Daniel J. McCormick

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Two series of overlapping peptides comprising the entire sequences of the β-subunits of human lutropin (LH) and choriogonadotropin (hCG) were prepared by a comprehensive synthetic strategy in order to identify all linear regions of the subunit that may participate in binding of the hormone to its receptor. Each series of peptides (15 residues in length) spanned the entire amino acid sequences of the two β-subunits. The peptides were tested for their ability to inhibit the binding of 125I-labeled hCG or LH to rat ovarian membranes and for their ability to inhibit hCG-stimulated progesterone production in a Leydig cell bioassay. The most potent inhibitor of LH/ hCG binding was a peptide containing the sequence β81-95, a receptor binding site of the LH/hCG β subunit not previously described. The concentration at which LH/hCG binding was inhibited at 50% (IC50) was 20 μM and 30 μM for hCGβ 81-95 and LHβ 81-95, respectively. These peptides also inhibited the stimulation of progesterone production by hCG in Leydig cell bioassays. In order to determine important residues that inhibit binding within this region, a third set of peptides was synthesized in which each residue of hCGβ 81-95 was sequentially replaced with the residue l-alanine. Five residues (Leu-86, Cys-88, Cys-90, Arg-94, and Arg-95) were critical for maximal inhibition of hCG binding by CGβ 81-95. In addition to site β81-95, other sites that inhibited hCG/LH binding but with significantly lower potencies included hCGβ 1-15, LHβ 41-55, and LHβ 91-105. These results affirm the presence of several binding regions in the LH/hCG β-subunit prominent among which is the sequence β81-95. This region represents a previously unidentified binding site of high inhibitory activity and contains at least 5 residues important for maximal interaction with the LH/ hCG receptor.

Original languageEnglish (US)
Pages (from-to)173-181
Number of pages9
JournalMolecular and Cellular Endocrinology
Issue number1-2
StatePublished - Nov 1993


  • Gonadotropin
  • Hormone peptide
  • LH
  • Receptor binding
  • hCG

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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