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 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.

Expression of activin and follistatin in the rat hypothalamus: anatomical association with gonadotropin-releasing hormone neurons and possible role of central activin in the regulation of luteinizing hormone release.

The central role of activin in the regulation of the reproductive axis remains largely unexplored. Evidence suggests that activin may play a role in control-linggonadotropin-releasing hormone (GnRH) release. We assessed potential neuroanatomical associations between activin- and GnRH-neuronal systems via examination of the distribution of activin betaA-subunit and activin binding protein (follistatin) protein and mRNA signals relative to GnRH neurons in the adult rat brain. Activin betaA-subunit-immunostained fibers were distributed throughout the hypothalamus and GnRH-positive perikarya, and fibers were in close association with betaA-subunit-immunoreactive fibers. Follistatin mRNA-expressing cells were also identified throughout the hypothalamus with GnRH fibers often observed juxtaposed to follistatin cell bodies. Colocalization of either the betaA-subunit or follistatin within GnRH neurons was not detected. The functional significance of central activin in the regulation of the reproductive axis was also demonstrated. The intracerebroventricular infusion of rh-activin A significantly increased luteinizing hormone, but not follicule-stimulating hormone, serum levels in adult male rats. Taken together, the present results support an interaction between activin and GnRH neuronal systems in the rat hypothalamus, and suggest activin may act within the brain to regulate the reproductive axis.