Clinical manifestations of impaired GnRH neuron development and function

Hyung Goo Kim, Balasubramanian Bhagavath, Lawrence C. Layman

Research output: Contribution to journalReview article

39 Scopus citations

Abstract

Gonadotropin-releasing hormone (GnRH) and olfactory neurons migrate together in embryologic development, and disruption of this process causes idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome (KS)). Patients with IHH/KS generally manifest irreversible pubertal delay and subsequent infertility due to deficient pituitary gonadotropins or GnRH. The molecular basis of IHH/KS includes genes that: (1) regulate GnRH and olfactory neuron migration; (2) control the synthesis or secretion of GnRH; (3) disrupt GnRH action upon pituitary gonadotropes, or (4) interfere with pituitary gonadotropin synthesis or secretion. KS patients may also have midline facial defects indicating the diverse developmental functions of genes involved. Most causative genes cause either normosmic IHH or KS except FGFR1, which may cause either phenotype. Recently, several balanced chromosomal translocations have been identified in IHH/KS patients, which could lead to the identification of new disease-producing genes. Although there are two cases reported who have digenic disease, this awaits confirmation in future larger studies. The challenge will be to determine the importance of these genes in the 10-15% of couples with normal puberty who have infertility.

Original languageEnglish (US)
Pages (from-to)165-182
Number of pages18
JournalNeuroSignals
Volume16
Issue number2-3
DOIs
StatePublished - Feb 1 2008

Keywords

  • GnRH neuron migration
  • Gonadotropin deficiency
  • Gonadotropin-releasing hormone
  • Hypogonadism
  • Idiopathic hypogonadotropic hypogonadism
  • Kallmann syndrome
  • Olfactory neuron migration

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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