title: The adult pituitary shows stem/progenitor cell activation in response to injury and is capable of regeneration.
abstract: The pituitary gland constitutes, together with the hypothalamus, the regulatory core of the endocrine system. Whether the gland is capable of cell regeneration after injury, in particular when suffered at adult age, is unknown. To investigate the adult pituitary's regenerative capacity and the response of its stem/progenitor cell compartment to damage, we constructed a transgenic mouse model to conditionally destroy pituitary cells. GHCre/iDTR mice express diphtheria toxin (DT) receptor after transcriptional activation by Cre recombinase, which is driven by the GH promoter. Treatment with DT for 3 d leads to gradual GH(+) (somatotrope) cell obliteration with a final ablation grade of 80-90% 1 wk later. The stem/progenitor cell-clustering side population promptly expands after injury, concordant with the immediate increase in Sox2(+) stem/progenitor cells. In addition, folliculo-stellate cells, previously designated as pituitary stem/progenitor cells and significantly overlapping with Sox2(+) cells, also increase in abundance. In situ examination reveals expansion of the Sox2(+) marginal-zone niche and appearance of remarkable Sox2(+) cells that contain GH. When mice are left after the DT-provoked lesion, GH(+) cells considerably regenerate during the following months. Double Sox2(+)/GH(+) cells are observed throughout the regenerative period, suggesting recovery of somatotropes from stem/progenitor cells, as further supported by 5-ethynyl-2'-deoxyuridine (EdU) pulse-chase lineage tracing. In conclusion, our study demonstrates that the adult pituitary gland holds regenerative competence and that tissue repair follows prompt activation and plausible involvement of the stem/progenitor cells.
authors.affiliation: Laboratory of Tissue Plasticity, Research Unit of Embryo and Stem Cells, Department of Development and Regeneration, University of Leuven (Katholieke Universiteit Leuven), Campus Gasthuisberg (O&N1), Herestraat 49, B-3000 Leuven, Belgium.
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Fu
authors.forename: Lies
authors.initials: L
authors.lastname: Gremeaux
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
authors.forename: Daisy
authors.initials: D
authors.lastname: Liekens
authors.forename: Jianghai
authors.initials: J
authors.lastname: Chen
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buch
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Rhonda
authors.initials: R
authors.lastname: Kineman
authors.forename: Hugo
authors.initials: H
authors.lastname: Vankelecom
mesh_terms: D000818:Animals; D019070:Cell Lineage; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012038:Regeneration; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors
chemical_list: C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D013006:Growth Hormone; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine