Endocrine Abstracts

The hypothalamic-pituitary-adrenal axis is a major regulation of inflammation via the release of adrenal glucocorticoids. We recently showed that anaphylatoxin C3a receptors are expressed throughout the anterior pituitary gland and that immune-derived complement C3a and its less active derivative, C3adesR (loss of C-terminal arginine) are potent stimuli for pituitary hormones.

In this study we investigated the expression of the anaphylatoxin receptor C5a and of a related, but reportedly non-signalling, receptor C5L2 in the anterior pituitary gland. C5a is a potent pro-inflammatory compound that is rapidly cleaved to C5adesR; C5L2, in contrast to the C5a receptor, binds both native C5a and C5adesR with high affinity.

Using RT-PCR, mRNA for the C5a receptor and for C5L2 was detected in rodent anterior pituitary tissue and in all rodent pituitary cell lines. Immunofluorescent immunocytochemistry data paralleled that for RT-PCR and showed strong expression of the C5a receptor, but relatively weak expression of C5L2. Using MMQ (prolactin secreting) cells we showed that exogenously added murine C5a (1-100 nanomolar) but not C5adesR stimulated ERK and p38 MAPK phosphorylation with a peak time of around 30 minutes. Similar concentrations of C5a (up to 4 days exposure) had no effect on MMQ proliferation as determined using the MTS proliferation assay (formazan production by metabolically active cells). C5a however did inhibit the expression (Western analysis) of connexin-43 within 1 hour of exposure in MMQ cells.

In summary we have shown that the C5a receptor and C5L2 is expressed throughout the cells (both endocrine and folliculostellate) of the anterior pituitary gland. C5a also appears to be an inhibitor of gap junction formation which may be mediated by ERK or p38 MAPK phosphorylation.