Endocrine Abstracts

Complement C5a is associated with various pro-inflammatory effects such as chemotaxis, production of superoxides, histamine release, vasodilatation and smooth muscle contraction. In sepsis, excessive production of C5a can lead to multi-organ failure. C5a mediates its actions through the C5a receptor (C5aR) but may also bind to a second receptor called C5L2 that acts as a decoy for removing excess C5a. C5a is also rapidly cleaved to a less active form, C5adesR; C5L2, in contrast to C5aR, binds both C5a and C5adesR with high affinity. In this report we show that the anterior pituitary gland expresses C5a and C5L2 receptors and that C5a activates ERK and AKT phosphorylation but inhibits MIF secretion.

Using RT-PCR, C5aR and C5L2 mRNA were detected in rodent anterior pituitary tissue and in all of the rodent pituitary cell lines used. Immunofluorescent immunocytochemistry showed strong expression of C5aR, but relatively weak expression of C5L2. Western analysis of MMQ (prolactin secreting) and TtT/GF (folliculostellate) cells showed that exogenously added recombinant murine C5a (1–100 nM) but not C5adesR stimulated ERK and AKT phosphorylation with a peak time of around 30 minutes. However C5a and C5adR, dose dependently, inhibited MIF (as measured by ELISA) secretion in MMQ, GH3 and AtT-20 cells; at 70 nM inhibition was respectively 35–45% (P<0.001), 45–55% (P<0.001) and 35–45% (P<0.001). In summary we have shown that functional C5a and C5L2 receptors are expressed in many cell types of the anterior pituitary gland and C5a and C5adR both inhibit MIF secretion by, as yet, an unknown mechanism. The presence of C5a (and of C3a) receptors in the anterior pituitary gland suggest that immune-derived molecules may regulate the HPA axis to limit inflammation.