GENES REGULATING HYPOTHALAMIC AND PITUITARY DEVELOPMENT

Several pituitary transcription factors have been identified in the la st 3 years. They offer new insights into the processes that direct org anogenesis, cell commitment, proliferation and differentiated function . All are DNA-binding proteins, but they have ties to different famili es of homeodomain proteins. They differ in their distribution and in t he timing of their appearance and extinction. The Rathke's pouch homeo box protein (Rpx) has a paired-like homeodomain. In mice, it appears o n embryonic day 8.5 (day e8.5) and is gone by day e14.5. Its targets f or activation are unknown. Pituitary OTX has a tryptophan-phenylalanin e-lysine motif in its homeodomain. It appears early and persists. It s hows independent activation of the alpha-glycoprotein subunit (alpha-G SU) and pro-opiomelanocortin genes and co-operates with Pit-1 in activ ation of the growth hormone and prolactin genes. Pituitary Lim (P-Lim) protein also acts independently on the alpha-GSU gene, and acts in co ncert with Pit-1 to activate other genes. A fourth protein, termed the 'Prophet of Pit-1', or Prop-1, is the recently discovered cause of Am es dwarfism in mice. This paired-like protein is necessary for the sub sequent expression of Pit-1 in somatotrophs, lactotrophs and thyrotrop hs. Any or all of the newly discovered pituitary genes are candidates for mutations causing hypopituitarism in humans. As several are expres sed transiently in tissues other than the pituitary during organogenes is, the phenotypes produced by mutations in these genes may prove to b e complex.