Pax6 is implicated in murine pituitary endocrine function

Pax6, an evolutionarily conserved transcription factor, is expressed in the murine and zebrafish embryonic pituitary, but its role in pituitary develo pment and endocrine function has not been described, To study the role of P ax6 in vivo, we examined Pax6 mutant mouse (Sey(Neu)) pituitaries. Mice hom ozygous for the Sey(Neu) mutation die at birth; therefore, we examined pept ide hormone expression by the differentiated pituitary cell types as well a s 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 e xpression of these peptide hormones is present, as is expression of other p ituitary markers. This suggests that pituitary cell types are able to diffe rentiate in mutant embryos, To identify the cellular or physiologic mechani sm responsible for less GH- and PRL-immunoreactivity in Pax6 mutant mice, w e tested serum levels of GH and PRL, Pax6 homozygous mutant mice have CH se rum levels one fifth that of controls at embryonic d 17.5, and one-third th at of controls at postnatal d 0, PRL serum levels, which are very low durin g embryonic and neonatal stages, were below assay detection limits in both the wild-type and mutant groups. Taken together, these data suggest that Pa x6 is not essential for pituitary differentiation, but rather functions to establish appropriate neonatal homeostatic levels of GH and PRL, possibly t hrough regulation of translational or secretory mechanisms.