Molecular analysis of LHX3 and PROP-1 in pituitary hormone deficiency patients with posterior pituitary ectopia

Kyle W. Sloop, Emily Walvoord, Aaron D. Showalter, Ora H. Pescovitz, Simon Rhodes

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The cause of posterior pituitary ectopia associated with anterior pituitary hormone deficiencies is unknown. We describe children with combined pituitary hormone deficiency (CPHD) or isolated GH deficiency. In all cases, magnetic resonance imaging examination revealed abnormal pituitary gland development featuring ectopic posterior lobe location and frequently hypoplastic anterior lobes. Embryonic development of the pituitary requires the coordinated expression of specific transcription factors. Mutations of the PIT-1 and PROP-1 transcription factors are responsible for CPHD in some patients with normally positioned posterior pituitaries. In mice, the Lhx3 LIM homeodomain transcription factor is required for both structural development and cellular differentiation of the pituitary gland. Thus, we hypothesized that mutations in one or both of the two human LHX3 isoforms are responsible for posterior pituitary ectopia associated with anterior pituitary hypopituitarism. Comprehensive molecular analysis of the LHX3 isoforms was performed to test this hypothesis. No loss of function mutations in the LHX3 gene were detected. In addition, analysis of PROP-1 did not reveal mutations that might cause this phenotype. These studies suggest that the abnormal processes leading to the development of CPHD or GH deficiency associated with posterior pituitary ectopia are not a result of aberrant LHX3 or PROP-1 function, but may be caused by defects at other gene loci.

Original languageEnglish
Pages (from-to)2701-2708
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume85
Issue number8
DOIs
StatePublished - 2000

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Pituitary Hormones
Transcription Factors
Mutation
Protein Isoforms
Pituitary Gland
Genes
Anterior Pituitary Hormones
Pituitary Dwarfism
Magnetic resonance
Hypopituitarism
Embryonic Development
Imaging techniques
Defects
Magnetic Resonance Imaging
Phenotype
Combined Pituitary Hormone Deficiency

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Molecular analysis of LHX3 and PROP-1 in pituitary hormone deficiency patients with posterior pituitary ectopia. / Sloop, Kyle W.; Walvoord, Emily; Showalter, Aaron D.; Pescovitz, Ora H.; Rhodes, Simon.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 85, No. 8, 2000, p. 2701-2708.

Research output: Contribution to journalArticle

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