Purpose of review: To discuss pituitary development and function related to those factors in which molecular defects resulting in combined pituitary hormone deficiency have been described in humans, and to describe recently reported novel mutations in these factors (January 2010 to September 2011).
Recent findings: Novel mutations have been found in transcription factors involved in pituitary development, HESX1; LHX3; LHX4; SOX3; Prophet of Pit-1; and POU1FI, and in some of the signaling molecules expressed in the ventral diencephalon (fibroblast growth factor 8 and GLI2). There is phenotypic variability for the same mutation suggesting variable penetrance due to other genetic, epigenetic, or environmental factors. The incidence of mutations in these factors is low suggesting that other genes or environmental factors are responsible for the majority of cases of combined pituitary hormone deficiency.
Summary: Development of the pituitary gland and pituitary cell determination and specification depend on the expression and interaction of signaling molecules and transcription factors in overlapping, but distinct, spatial and temporal patterns. Studying genotype-phenotype correlations in patients with mutations in these factors give insight into the mechanisms involved in normal pituitary development and function.