title: Pituitary phenotypes of mice lacking the notch signalling ligand delta-like 1 homologue.
abstract: The Notch signalling pathway ligand delta-like 1 homologue (Dlk1, also named Pref1) is expressed throughout the developing pituitary and becomes restricted to mostly growth hormone (GH) cells within the adult gland. We have investigated the role of Dlk1 in pituitary development and function from late embryogenesis to adulthood using a mouse model completely lacking the expression of Dlk1. We confirm that Dlk1-null mice are shorter and weigh less than wild-type littermates from late gestation, at parturition and in adulthood. A loss of Dlk1 leads to significant reduction in GH content throughout life, whereas other pituitary hormones are reduced to varying degrees depending on sex and age. Both the size of the pituitary and the proportion of hormone-producing cell populations are unchanged, suggesting that there is a reduction in hormone content per cell. In vivo challenge of mutant and wild-type littermates with growth hormone-releasing hormone and growth hormone-releasing hexapeptide shows that reduced GH secretion is unlikely to account for the reduced growth of Dlk1 knockout animals. These data suggest that loss of Dlk1 gives rise to minor pituitary defects manifesting as an age- and sex-dependent reduction in pituitary hormone contents. However, Dlk1 expression in other tissue is most likely responsible for the weight and length differences observed in mutant animals.
authors.affiliation: Division of Molecular Neuroendocrinology, MRC National Institute for Medical Research, London, UK.
authors.forename: L Y M
authors.initials: LY
authors.lastname: Cheung
authors.forename: K
authors.initials: K
authors.lastname: Rizzoti
authors.forename: R
authors.initials: R
authors.lastname: Lovell-Badge
authors.forename: P R
authors.initials: PR
authors.lastname: Le Tissier
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D005260:Female; D006128:Growth / Q000235:genetics; D013006:Growth Hormone / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D051880:Receptors, Notch; D013006:Growth Hormone