Complement C3a receptors in the pituitary gland: a novel pathway by which an innate immune molecule releases hormones involved in the control of inflammation.
Two-way communication exists between the endocrine and immune systems using molecules such as hormones and cytokines. Here we describe a new pathway by which C3a, a complement-derived cytokine, stimulates anterior pituitary hormone release and activates the hypothalamic-pituitary-adrenal axis, a reflex central to the stress response and to the control of inflammation. We show that C3a receptors are expressed in pituitary hormone secreting and non-hormone secreting (folliculostellate) cells and that both C3a and C3adesArg (a non-inflammatory metabolite) stimulate pituitary cell cultures to release prolactin, growth hormone, and adrenocorticotropin. Serum levels of these hormones, together with adrenal corticosterone, increase dose dependently with recombinant C3a and C3adesArg administration in vivo. Pertussis toxin blocks the response to C3a but not C3adesArg, which indicates the presence of two receptors, only one of which is coupled to Galphai-proteins. We propose that the complement innate immune molecules (cytokines) modulate tissue-specific and systemic inflammatory responses through communication with the endocrine pituitary gland.
Francis
Karen
K
Brain Inflammation and Immunity Group, Department of Medical Biochemistry, University of Wales College of Medicine, Tenovus Bldg., Heath Park, Cardiff, CF14 4XN, UK.
Lewis
B Mary
BM
Akatsu
Hiroyasu
H
Monk
Peter N
PN
Cain
Stuart A
SA
Scanlon
Maurice F
MF
Morgan
B Paul
BP
Ham
Jack
J
Gasque
Philippe
P
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D015926:Complement C3a / Q000494:pharmacology; D004703:Endocrine System / Q000378:metabolism; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D008565:Membrane Proteins; D018448:Models, Immunological; D037342:Pertussis Toxin / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism*; D051381:Rats; D011951:Receptors, Complement / Q000378:metabolism*; D015398:Signal Transduction
D001798:Blood Proteins; D008565:Membrane Proteins; D010907:Pituitary Hormones; D011951:Receptors, Complement; C085567:complement C3a receptor; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D037342:Pertussis Toxin