PRL deficiency: PRL concentration is low in cases with POU1F1, LHX3
, OTX2 and IGFSF-1 gene mutations and in cases of panhypopituitarism.
Another group, using direct reprogramming, obtained human motor neurons from human fibroblasts, using a combination of factors Ascl1, Brn2, Myt1l, Lhx3
, Hb9, Isl1, Ngn2, and NEUROD1 .
Transcription factor genes playing a role in the development of hypothalamus and pituitary are pituitary transcription factor 1 (PIT1), Prophet of Pit-1 (PROP1), LIM Homeobox 3 (LHX3), LIM Homeobox 4 (LHX4), and HESX Homeobox 1 (HESX1) which all are known to be important for organ commitment and embryonic pituitary cell differentiation.
CPHD occurs due to recognized mutations of transcription factors such as HESX1, PROP1, POU1F1, LHX3, and LHX4.
Early on in the process, two of the transcription factors, Isl1 and Lhx3, work in tandem, binding to the genome and beginning a cascade of events including changes to chromatin structure and gene expression in the cells.
Later in the transformation process, Isl1 and Lhx3 rely on changes in the cell initiated by Ngn2 to help complete the transformation.
Cells with continuous nuclear [beta]-catenin express Lhx3/4 (formerly called Lhx3
) at the 32-cell stage, which is an essential factor for endoderm specification in the embryo of the closely related species Ciona savignyi.
Rhodes, "Developmental analysis and influence of genetic background on the lhx3
w227ter mouse model of combined pituitary hormone deficiency disease," Endocrinology.
, Lhx4, Prop-1 ve POU1F1 (Pit 1) mutasyonlari coklu hormon eksikliklerine neden olurken Hesx1 (septooptik displazi-SOD), Pitx2 (Rieger sendromu) gibi diger mutasyonlar spesifik sendromlara yol acarlar (11).
Alterations in pituitary development genes, such as PIT1, PROP1, HESX1, LHX3
, LHX4, and SOX3 can result in CCH and multiple pituitary hormone deficiencies (1).
The most commonly recognized genetic defects associated with CPHD include mutations within PROP1, POU1F1, HESX1, LHX3
, LHX4, OTX2, GLI2, and SOX3.
HESX1, POU1F1, PROP1, LHX4, LHX3
, and OTX2 genes have been associated with combined pituitary hormone deficiencies to date.