Cellular localization of apelin and its receptor in the anterior pituitary: evidence for a direct stimulatory action of apelin on ACTH release.
Apelin is a bioactive peptide recently identified as the endogenous ligand of the human orphan G protein-coupled receptor APJ. The presence of apelin-immunoreactive nerve fibers, together with the detection of apelin receptor mRNA in the parvocellular part of the paraventricular nucleus and the stimulatory action of apelin on corticotropin-releasing hormone release, indicate that apelin modulates adrenocorticotropin (ACTH) release via an indirect action on the hypothalamus. However, a direct action of apelin in the anterior pituitary cannot be excluded. Here, we provided evidence for the existence of an apelinergic system within the adult male rat pituitary gland. Double immunofluorescence staining indicated that apelin is highly coexpressed in the anterior pituitary, mainly in corticotrophs (96.5 +/- 0.3%) and to a much lower extent in somatotropes (3.2 +/- 0.2%). Using in situ hybridization combined with immunohistochemistry, a high expression of apelin receptor mRNA was also found in corticotrophs, suggesting a local interaction between apelin and ACTH. In an ex vivo perifusion system of anterior pituitaries, apelin 17 (K17F, 10(-6) M) significantly increased basal ACTH release by 41%, whereas apelin 10 (R10F, 10(-6) M), an inactive apelin fragment, was ineffective. In addition, K17F but not R10F induced a dose-dependent increase in K(+)-evoked ACTH release, with maximal increase being observed for a 10(-6) M concentration. Taken together, these data outline the potential role of apelin as an autocrine/paracrine-acting peptide on ACTH release and provide morphological and neuroendocrine basis for further studies that explore the physiological role of apelin in the regulation of anterior pituitary functions.
Reaux-Le Goazigo
Annabelle
A
Institut National de la Santé et de la Recherche Médicale, Unité 691, Collège de France, 11 Place Marcelin Berthelot, Paris, France.
Alvear-Perez
Rodrigo
R
Zizzari
Philippe
P
Epelbaum
Jacques
J
Bluet-Pajot
Marie-Thérèse
MT
Llorens-Cortes
Catherine
C
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D052680:Corticotrophs / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008954:Models, Biological; D010446:Peptide Fragments / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D014018:Tissue Distribution
D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; D043562:Receptors, G-Protein-Coupled; D000324:Adrenocorticotropic Hormone