Formyl peptide receptor ligands exert differential effects on corticosterone secretion from the hypothalamo‐pituitary‐adrenal (HPA) axis

Abstract

The stress response results in increased secretion of cortisol in man and corticosterone (CORT) in rodents. Our previous studies have identified roles for annexin A1 (ANXA1) and its receptor, a member of the formyl peptide receptor (FPR) family (possibly Fpr2) within the hypothalamus and pituitary gland in regulating CORT secretion. The FPRs are expressed in abundance in the adrenal gland but their role has not been determined. We hypothesised that FPRs contribute to the local mechanisms regulating CORT release. Adrenal glands from male Wistar rats (n = 6, 220 – 250 g) were dispersed in Earle's balanced salt solution (EBSS) and collagenase (95% O2, 5% CO2, 37 °C, 2 h) then stimulated (4 h) with a submaximal concentration of ACTH1–24 [Tetracosactide, 10−7 mol.L−1] in the presence and absence of various FPR ligands. ACTH stimulation resulted in a 60% increase in CORT release (P < 0.001). Versus basal release, fMLF (Fpr1), Ac2–26 (Fpr2/3), and 15‐epi‐LXA4 (Fpr3) were inhibitory, whereas F2L (Fpr2) was stimulatory (P < 0.001). Versus ACTH alone, ACTH‐stimulated CORT release was reduced in cells treated with fMLF [10−7], peptide Ac2–26 [10−7], and 15‐epi‐LXA4 [10−9] by 80%, but was increased in the presence F2L [10−10] by 50% (P < 0.001). Our work showed certain Fpr1/Fpr3 agonists inhibit adrenal CORT release whereas Fpr2 appears to be stimulatory.This was funded by the BBSRC.