Response to challenge with gonadotropin-releasing hormone agonist in a mother and her two sons with a constitutively activating mutation of the luteinizing hormone receptor - A clinical research center study

Ira M. Rosenthal*, Samuel Refetoff, Barry Rich, Randall B. Barnes, Thongkum Sunthornthepvarakul, Jasmine Parma, Robert L. Rosenfield

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

The pituitary-gonadal axis was evaluated in a mother after two of her sons with familial male-limited pseudoprecocious puberty were found to have a constitutively activating mutation of the LH receptor (LHR). Genotyping demonstrated that all showed a mutation in one of the two alleles, a substitution of Gly for Asp578 in the sixth transmembrane segment of the LHR. Ovarian function was normal in the 36-yr-old mother as assessed by LH dynamics and FSH and androgen levels throughout the menstrual cycle. Hormonal responses to acute GnRH agonist (nafarelin) challenge, chronic GnRH agonist administration, and dexamethasone were also normal. Studies of the boys upon presentation at 2.4 and 3.5 yr of age revealed that acute LH responses to nafarelin were in the hypogonadotropic range, and the FSH responses were prepubertal despite the presence of late pubertal testosterone blood levels. Upon the inception of true puberty at 11 yr of age in the older brother, gonadotropin responses normalized for the state of development. The data show that this activating LHR mutation does not cause functional ovarian hyperandrogenism and causes only incomplete pubertal activation of Leydig cells. The results are compatible with relatively low constitutive activity associated with this structural abnormality of LHR.

Original languageEnglish (US)
Pages (from-to)3802-3806
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume81
Issue number10
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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