Several genes in the Wnt, Notch and Shh signalling pathways related to hypothalamic-pituitary development, such as PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF and HESX1, have been found to be associated with PSIS.
In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis.
The transcription factor pituitary-1 (Pit-1) is mainly expressed in the pituitary gland, where it has critical roles in cell differentiation and as a transcriptional factor for GH and prolactin (PRL).
The characterization of pathological lesions in several other pituitary-expressed genes that are epistatic to GH1 (POU1F1, PROP1 and GHRHR) has identified additional causes of GH deficiency, the molecular genetics of which are also explored.
The transcription factor pituitary-1 (Pit-1) is a homeodomain-containing protein that is expressed mainly in the pituitary, where it drives the expression of growth hormone, prolactin, and thyroid-stimulating hormone beta chain genes.
Transcriptional induction of the human renin gene by cyclic AMP requires cyclic AMP response element-binding protein (CREB) and a factor binding a pituitary-specific trans-acting factor (Pit-1) motif.