Inherited disorders of the gonadotropin hormones

John C. Achermann, Jeffrey Weiss, Eunjig Lee, J. Larry Jameson

Research output: Contribution to journalReview article

54 Citations (Scopus)

Abstract

Pulsatile GnRH acts at the GnRH receptor on gonadotropes to stimulate gonadotropin gene expression, hormone synthesis and secretion. The pituitary gonadotropins, LH and FSH, stimulate steroid production and gametogenesis in males and in females. Gonadotropin production thus requires the normal development and function of hypothalamic GnRH-producing neurons and pituitary gonadotrope cells. Genes involved in gonadotrope development and/or gene expression include SF1, DAX1, KAL, GNRHR, PC1, HESX1, LHX3, PROP1, LHβ, and FSHβ. Given the complex control of gonadotropin biosynthesis and secretion, it is not surprising that genetic abnormalities have been identified at several of these steps. Some of the mutations that will be reviewed include: (1) SF1 and DAX1-orphan nuclear receptors that are expressed at multiple levels throughout the reproductive axis; (2) KAL-X-linked Kallmann syndrome, where there is abnormal development of hypothalamic GnRH-producing neurons; (3) PC1-causing abnormal processing of GnRH and GNRHR mutations that impair action at the GnRH receptor; (4) HESX1, LHX3, PROP1-abnormal development/function of the gonadotrope cell lineage; (5) LHβ and FSHβ-mutations in the gonadotropin genes that cause structural abnormalities in the hormones. Although all of these gene defects lead to gonadotropin deficiency, each disorder is associated with unique phenotypic or hormonal features. Characterization of the molecular basis of gonadotropin deficiency is useful for directing therapy and for genetic counseling. Identification of these mutations also provides insight into the pathways that govern reproduction.

Original languageEnglish
Pages (from-to)89-96
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume179
Issue number1-2
DOIs
Publication statusPublished - 2001 Jun 20

Fingerprint

Gonadotropins
Hormones
Gonadotropin-Releasing Hormone
LHRH Receptors
Mutation
Genes
Gene expression
Neurons
Kallmann Syndrome
Orphan Nuclear Receptors
Gametogenesis
Pituitary Gonadotropins
Gene Expression
Biosynthesis
Genetic Counseling
Cell Lineage
Reproduction
Steroids
Defects
Processing

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Achermann, John C. ; Weiss, Jeffrey ; Lee, Eunjig ; Jameson, J. Larry. / Inherited disorders of the gonadotropin hormones. In: Molecular and Cellular Endocrinology. 2001 ; Vol. 179, No. 1-2. pp. 89-96.
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Inherited disorders of the gonadotropin hormones. / Achermann, John C.; Weiss, Jeffrey; Lee, Eunjig; Jameson, J. Larry.

In: Molecular and Cellular Endocrinology, Vol. 179, No. 1-2, 20.06.2001, p. 89-96.

Research output: Contribution to journalReview article

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