A case of male-limited precocious puberty caused by a point mutation in the second transmembrane domain of the luteinizing hormone choriogonadotropin receptor gene.

We describe a Japanese patient with male-limited precocious puberty who has a heterozygous thymine to cytosine (T to C) transition at nucleotide 1193; the mutation encodes a methionine to threonine substitution in residue 398 (M398T) of transmembrane helix 2 of the luteinizing hormone/choriogonadotropin receptor. Transfected into COS-7 cells, M398T exhibited constitutively high basal cAMP levels but retained an agonist-induced cAMP response. The constitutively higher cAMP levels caused by M398T are consistent with Leydig cell activation and precocious puberty in the patient. By comparison to wild type receptor, M398T transfectants have significantly lower agonist-induced inositol phosphate (IP) levels at > 10(-10) M hCG concentrations and a higher apparent affinity for binding hCG. These data suggest that the M398T substitution alters Gq coupling and phospholipase-C activation, as well as Gs, coupling and adenylyl cyclase activity, and changes the conformation of the extracellular domain of the receptor.

• Publication year

  1996

• Venue

  Biochemical and Biophysical Research Communications - BBRC

• Publication date

  1996-03-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1006/BBRC.1996.0528PMID 8607787
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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