A missense mutation in the second transmembrane segment of the luteinizing hormone receptor causes familial male-limited precocious puberty

Journal Article · Sun Oct 01 04:00:00 EDT 1995 · Journal of Clinical Endocrinology and Metabolism

DOI:https://doi.org/10.1210/jc.80.11.3168· OSTI ID:443618

Kraaij, R; Post, M; Grootegoed, J A ^[1]

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1. Erasmus Univ. Rotterdam (Netherlands); and others

Patients with familial male-limited precocious puberty present with early onset of puberty. Several missense mutations in the LH receptor gene that cause amino acid substitutions in the sixth transmembrane segment of the receptor protein have been shown to be a cause of the disorder. We have identified a novel LH receptor gene mutation in a patient with familial male-limited precocious puberty that results in a threonine for methionine substitution at position 398 in the second transmembrane segment of the receptor protein. In vitro expression in human embryonic kidney 293 cells of this LH receptor mutant and two previously described LH receptor mutants showed that cAMP production in the absence of hormone was elevated up to 25-fold compared to the basal level of the wild-type receptor. The ED{sub 50} values of hormone-induced cAMP production was relatively low for mutant receptors. We also produced receptors containing amino acid substitutions in both the second and sixth transmembrane segments. For these double mutants, basal receptor activities were similar to the basal activities observed in single mutants, whereas hormone-induced receptor activation was almost completely abolished. 31 refs., 2 figs.

• OSTI ID: 443618
• Journal Information: Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 10 Vol. 80; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACIDS
DOMINANT MUTATIONS
GENE MUTATIONS
GENES
GTP-ASES
HEREDITARY DISEASES
LH
MALES
POLYMERASE CHAIN REACTION
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
UROGENITAL SYSTEM DISEASES