Endocrine Abstracts

Introduction: The N-formyl peptide receptor (FPR) family of G-protein-coupled receptors, originally identified to recognise N-formylated bacterial peptides, has in more recent times been shown to bind annexin-1 (ANXA1). ANXA1 is a signalling molecule well demonstrated to mediate two key glucocorticoid effects in the anterior pituitary: inhibition of ACTH release from corticotrophs and regulation of cell proliferation. Whilst previous RT-PCR studies have detected Fpr2, Fpr3, Fpr-rs6 and Fpr-rs7 receptor mRNA in murine pituitary tissue, the specific member(s) of the FPR family involved in ANXA1 signalling are unclear. In this study, we investigated whether glucocorticoid inhibitory feedback is impaired in Fpr2/Fpr3 double knockout (DKO) mice.

Method: Anterior pituitary tissue from WT and Fpr2/Fpr3 DKO male mice was fixed and examined i) by electron microscopy to determine corticotroph size, granule morphology and rough endoplasmic reticulum (rER) expansion, and ii) by immunocytochemistry to determine corticotroph density. Plasma ACTH and corticosterone concentrations were determined by RIA.

Results: In Fpr2/Fpr3 DKO mice, corticotrophs exhibited a significant (P<0.01) increase in rER expansion and a significant (P<0.05) decrease in granule density (%) suggesting increased ACTH synthesis and secretion corresponding with elevated levels of plasma ACTH (P<0.05) and corticosterone (P<0.05). Fpr2/Fpr3 DKO mice exhibited a significant (P<0.01) increase in corticotroph cell density.

Conclusion: These data suggest that there is a loss of ANXA1-mediated glucocorticoid action in Fpr2/Fpr3 DKO mice, indicating that Fpr2 and/or Fpr3 may function as ANXA1 receptor(s) in the anterior pituitary.