Autoimmune hypophysitis of SJL mice: Clinical insights from a new animal model

Shey-Cherng Tzou, Isabella Lupi, Melissa Landek, Angelika Gutenberg, Ywh Min Tzou, Hiroaki Kimura, Giovanni Pinna, Noel R. Rose, Patrizio Caturegli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Autoimmune hypophysitis (AH) is a rare but increasingly recognized disease of the pituitary gland. Its autoantigens are unknown, and the management is difficult because it is often misdiagnosed as a nonsecreting adenoma. By immunizing female SJL/J mice with mouse pituitary extracts, we established a new mouse model of experimental AH. Immunized mice developed severe lymphocytic infiltration in the anterior pituitary that closely mimicked the human pathology. In the early phase of experimental AH, the pituitary enlarged, consistent with the compression symptoms reported by hypophysitis patients at presentation. In the florid phase, adrenal insufficiency and pituitary antibodies developed, in strong correlation with the pituitary pathology. In the late phase, hypothyroidism ensued, and the pituitary gland became atrophic. Using immune sera as probes in a two-dimensional immunoblotting screen followed by mass spectrometry, we identified several proteins that could function as pituitary autoantigens. These findings provide new insights into the pathogenesis of AH, and establish a platform for developing novel diagnostic biomarkers and therapeutics.

Original languageEnglish
Pages (from-to)3461-3469
Number of pages9
JournalEndocrinology
Volume149
Issue number7
DOIs
StatePublished - 1 Jul 2008

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