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1 Institut National de la Sante et de la Recherche Medicale, Unite 691, College de France, Paris, France
2 Institut National de la Sante et de la Recherche Medicale, Unite 549, Centre Paul Broca, Paris, France
* To whom correspondence should be addressed. E-mail: c.llorens-cortes{at}college-de-france.fr.
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 (PVN) and the stimulatory action of apelin on corticotropin-releasing hormone (CRH) release indicate that apelin modulates adrenocorticotropin (ACTH) release via an indirect action on the hypothalamus. However, a direct action of apelin in 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 co-expressed 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 to 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, 10-6M) significantly increased by 41 % basal ACTH release, whereas apelin 10 (R10F, 10-6M), an inactive apelin fragment, was ineffective. In addition, K17F but not R10F induced a dose-dependent increase in K+-evoked ACTH release; maximal increase being observed for a 10-6M 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 exploring the physiological role of apelin in the regulation of anterior pituitary functions.
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