title: LHX3 and LHX4 transcription factors in pituitary development and disease.
abstract: The LHX3 and LHX4 LIM-homeodomain proteins are regulatory transcription factors that play overlapping but distinct functions during the establishment of the specialized cells of the mammalian pituitary gland and the nervous system. Recent studies have identified a variety of mutations in the LHX3 and LHX4 genes in patients with combined pituitary hormone deficiency diseases. These patients have complex and variable syndromes involving short stature, metabolic disorders, reproductive system deficits, and nervous system developmental abnormalities. The short stature secondary to growth hormone deficiency is a key feature of the disorders associated with these gene mutations and responds well to supplementation with recombinant growth hormone. Overall, the frequency of mutations in the LHX3 and LHX4 genes in patients with combined pituitary hormone deficiency is low. Mutations in other regulatory genes such as HESX1, PROP1, PIT1 / POU1F1, and GLI2 have been shown to be additional causes of pituitary hormone deficiency, but overall, the etiology of many cases of hypopituitarism is not understood. Further investigation is therefore required to identify other genes, both primary regulatory genes and those with modifier functions, which contribute to pituitary development and function.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Colvin
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Mullen
authors.forename: Roland W
authors.initials: RW
authors.lastname: Pfaeffle
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Rhodes