Effect Of Transcription Factor ZBTB20 On Pituitary Development In Mice And Its Mechanism

Pituitary gland is an important part of the neuroendocrine system. As a hub of thehypothalamus and peripheral target organs, pituitary plays an important feature inmaintaining homeostasis, metabolism, growth and lactation. Pituitary development isa highly complex and precise process control. Multiple signaling pathways andtranscription factors activate or express in different space and time order. Any part ofa problem can lead to pituitary hypoplasia and the corresponding lack of the hormone.In recent years, according to the knockout mice and the human genealogy genemutation research, some transcription factors associated with pituitary developmenthave been found. At the same time, scientists also have got a certain understanding ofthe pituitary development’s regulation and control, but the molecular mechanism hasnot been fully clarified yet (1-6). Research progress and breakthrough in this field willrich people’s awareness of pituitary development process and pituitary functionregulation and there is a hope for new directions and methods for diagnosis andtreatment of pituitary related diseases.Zinc finger protein ZBTB20, the new member of BTB zinc finger proteinfamily, is also known as dendritic cells derived POZ zinc finger protein (Dendriticcell-derived POZ zinc finger, DPZF).It consists of741encoded amino acids,whose N terminus contains POZ domain (typically mediate protein-proteininteractions) and C terminus contains five C2H2zinc finger domain (usuallymediate the binding of DNA). It has30-40%homology with the known zinc POZBCL6and finger protein PLZF (7). ZBTB20widely expresses in a variety oftissues and organs such as brain, liver, pancreas, cartilage, etc. The knownphysiological functions include being involved in the expression ofalpha-fetoprotein in liver regulation, participating in the normal development ofhippocampal tissue, taking park in the regulation of pancreatic cells’functions(8-9). Although the molecular structure of ZBTB20is conservative andit’s function is important, awareness of its physiological function and mechanismof action in vivo is very limited. By the ZBTB20systemic knockout (ZBTB20-/-) mice model, we studied therole of transcription factor ZBTB20in pituitary growth development and it’smolecular mechanism through the ways of histology and molecular biologymethods.The results showed that, in normal mice, the expression of ZBTB20proteinin pituitary cells begins at the day of embryonic14.5(E14.5),and at E16.5,theexpression is almost near adulthood’s level, and will maintain a high expressionthroughout the life cycle. Zbtb20-/-mice pituitary volume is significantly reduced andin which the prolactin cells are missing accompanied by an undetectable prolactin(prolactin, PRL) expression and GH (growth hormone, GH) expression was reducedby a half. Through the target gland phenotypic analysis, we found that, Zbtb20-/-micepituitary hypoplasia major impact on growth and development by the decrease ofbody weight, breast development barriers by acinar duct extends hypoplasia andgonadal dysgenesis. Further research found that Zbtb20knockout mice’s embryo canstill differentiate pituitary GH/PRL double-positive precursor cells, but it can’tcontinue precursor cells differentiate into single positive PRL terminally differentiatedcells.Through those researches, we confirm the pituitary endocrine precursor cells orcell subsets witch ZBTB20worked on and find out that ZBTB20plays an importantrole in pituitary development of regulating lactotrophs’ final differentiation.It’s defectwill induce pituitary GH/PRL positive cells fail to differentiate directly to final PRLpositive cells.