Congenital pituitary hormone deficiencies: role of LHX3/LHX4 genes

Abstract

LHX3 and LHX4 are LIM domain transcription factors involved in the early steps of pituitary organogenesis. They are necessary for the proper differentiation of Rathke’s pouch that gives rise to the anterior pituitary lobe. Mutations of these transcription factors are involved in congenital hypopituitarism: to date, nine mutations of LHX3 have been reported, responsible for variable pituitary hormone deficiencies and extrapituitary manifestations, including limited neck rotation. By contrast, only five LHX4 mutations have been reported, responsible for variable hormone deficiencies, and pituitary/intracranial abnormalities. Future investigations will aim to better understand human pituitary organogenesis and to shed light on the interspecies differences in the roles of these transcription factors.

Keywords::

• combined pituitary hormone deficiencies
• congenital hypopituitarism
• haploinsufficiency
• LHX3
• LHX4
• pituitary transcription factors

Acknowledgements

The authors would like to thank participating patients and all clinicians who sent clinical data and samples for screening in the ‘Genhypopit’ database.

Financial & competing interests disclosure

The GENHYPOPIT network for the study of genetic determinants of hypopituitarism, coordinated by T Brue ([email protected]), was funded by the Groupement d’Intérêt Scientifique Institut des Maladies Rares (GISMR0201) and the Programe Hospitalier de Recherche Clinique (PHRC 25/2003, French Ministry of Health). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.