title: Pax6 is implicated in murine pituitary endocrine function.
abstract: Pax6, an evolutionarily conserved transcription factor, is expressed in the murine and zebrafish embryonic pituitary, but its role in pituitary development and endocrine function has not been described. To study the role of Pax6 in vivo, we examined Pax6 mutant mouse (SeyNeu) pituitaries. Mice homozygous for the SeyNeu mutation die at birth; therefore, we examined peptide hormone expression by the differentiated pituitary cell types as well as developmental marker expression in the intermediate and anterior lobes of the embryonic pituitary. GH- and PRL-immunopositive cells appear severely decreased in an outbred ICR background at embryonic d 17.5, although mRNA expression of these peptide hormones is present, as is expression of other pituitary markers. This suggests that pituitary cell types are able to differentiate in mutant embryos. To identify the cellular or physiologic mechanism responsible for less GH- and PRL-immunoreactivity in Pax6 mutant mice, we tested serum levels of GH and PRL. Pax6 homozygous mutant mice have GH serum levels one fifth that of controls at embryonic d 17.5, and one-third that of controls at postnatal d 0. PRL serum levels, which are very low during embryonic and neonatal stages, were below assay detection limits in both the wild-type and mutant groups. Taken together, these data suggest that Pax6 is not essential for pituitary differentiation, but rather functions to establish appropriate neonatal homeostatic levels of GH and PRL, possibly through regulation of translational or secretory mechanisms.
authors.affiliation: Department of Reproductive Medicine, University of California-San Diego, La Jolla, USA. cbentley@ucsd.edu
authors.forename: C A
authors.initials: CA
authors.lastname: Bentley
authors.forename: M P
authors.initials: MP
authors.lastname: Zidehsarai
authors.forename: J C
authors.initials: JC
authors.lastname: Grindley
authors.forename: A F
authors.initials: AF
authors.lastname: Parlow
authors.forename: S
authors.initials: S
authors.lastname: Barth-Hall
authors.forename: V J
authors.initials: VJ
authors.lastname: Roberts
mesh_terms: D000818:Animals; D015415:Biomarkers; D004268:DNA-Binding Proteins / Q000502:physiology*; D005136:Eye Proteins; D005838:Genotype; D013006:Growth Hormone / Q000097:blood; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010902:Pituitary Gland / Q000254:growth & development* / Q000502:physiology; D011388:Prolactin / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D012097:Repressor Proteins / Q000502:physiology*
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D011388:Prolactin; D013006:Growth Hormone