Involvement of pro-apoptotic and anti-apoptotic factors in the early development of the human pituitary gland
Mirna Saraga-Babic1, Mirna Bazina1, Katarina Vukojevic1,2, Ivana Bocina3 and Vedran Stefanovic4
1Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia, 2Department of Histology and Embryology, School of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina, 3Department of Biology, Faculty of Natural Sciences, University of Split, Split, Croatia and 4Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland.
Offprint requests to: Mirna Saraga-Babic, Department of anatomy, Histology and Embryology, School of Medicine, University of Split, Soltanska 2, 21000 Split, Croatia. e-mail: firstname.lastname@example.org
Summary. The spatial and temporal pattern of appearance of pro-apoptotic caspase-3 and p53 proteins, and anti-apoptotic bcl-2 protein was investigated in the developing pituitary gland of 6 human embryos 5-8-weeks old, using morphological and immuno-histochemical techniques. Their dynamic appearance was analyzed in the Rathke's pouch (future adenohypophysis), mesenchyme, and in the developing neurohypophysis. In the 5th and 6th week, caspase-3 positive cells appeared in the Rathke's pouch (5%) and stalk (11%), in the mesenchyme, but not in the neurohypophysis. In the 6th and 7th week, apoptotic cells were more numerous in the caudal part of the Rathke's pouch due to its separation from the oral epithelium. Pro-apoptotic p53 protein was detected in all parts of the pituitary gland throughout the investigated period. Nuclear condensations characterized cells positive to caspase-3 and p53 proteins. Apoptotic cells displayed condensations of nuclear chromatin on an ultrastructural level as well. While caspase-3 dependent pathway of cell death participated in morphogenesis of the adenohypophysis and associated connective tissue, p53-mediated apoptosis most likely participates in morphogenesis of all parts of the gland, including neurohypophysis. The anti-apoptotic bcl-2 protein was also detected in all parts of the developing gland. With advancing development, the positivity to bcl-2 protein increased in the cells of the adenohypophysis, while it decreased in the neurohypophysis. Bcl-2 protein probably prevented cell death in all parts of the gland and enhanced cell differentiation. The described pattern of appearance of the investigated pro-apoptotic and anti-apoptotic factors might be important for normal morphogenesis and function of the pituitary gland. Histol Histopathol 23, 1259-1268 (2008)
Key words: Human embryos, Caspase-3, p53, Bcl-2, pituitary gland