The hypothalamic pituitary adrenal (HPA) axis is the major regulator of stress and inflammation via the secretion of anti-inflammatory corticosteroids. This suggests an important bidirectional flow of information between the endocrine and immune systems. A critical component of the inflammatory response is the complement cascade in which anaphylatoxins C3a, C4a and C5a are released.
In this report we used colocalisation immunohistochemistry to show detailed expression of C3a receptor (C3aR) in the different cell types of the rat pituitary gland and primary anterior pituitary cultures to demonstrate that C3a is a potent stimulator of hormone release.
C3aR is strongly expressed in the intermediate and anterior lobes but not in the posterior lobe. In the anterior lobe C3aR colocalises with ACTH, Growth hormone, prolactin, TSHbeta and S100. Recombinant C3a dose dependently stimulates the secretion of prolactin (2-4 fold), growth hormone (4-9 fold) and ACTH ( <1 fold) but not TSH. Using 250nM C3a and an incubation time of four hours the hormone changes (expressed as % of basal) were for prolactin (338+/-11% p<0.001), growth hormone (683+/-69% p<0.001), ACTH (157+/-16% p<0.02) and TSH (87+/-17% n.s.). These effects of C3a were blocked in the presence of pertussis toxin.
These data show that C3aR colocalises with many of the hormone secreting cells and the non-hormone secreting folliculostellate cells of the pituitary gland. C3a also mediates hormone release either directly and/or indirectly during the inflammatory response. These data demonstrate novel complement C3a signalling pathways in the HPA axis suggesting that C3a may activate steroidogenesis during inflammation.
08 - 11 Apr 2002
British Endocrine Societies