Obestatin plays an opposite role in the regulation of pituitary somatotrope and corticotrope function in primates and mice
R. Luque1, J. Córdoba-Chacón1,2, C. Grande3, I. Gesmundo3, M. Gahete1,2, D. Gallo3, A. Pozo-Salas1, E. Ghigo3, R. Granata3, R. Kineman2 & J. Castaño1
Obestatin is a 23-amino acid amidated peptide that is encoded by the ghrelin gene and was therefore presumed to have regulatory effects on pituitary. However, the limited set of studies performed hitherto suggests that obestatin has no major effect on hormone secretion, in vivo or in vitro, from rodent pituitary, whereas no comparable data is still available on primates. Here, primary pituitary cell cultures from a non-human primate (baboon; Papio anubis) served to test the effects of obestatin (100 nM; 24 h) on the function of all pituitary cell types. Results revealed that obestatin did not alter expression or release of prolactin, LH, FSH or TSH. Conversely, obestatin treatment stimulated proopiomelanocortin (POMC) expression and ACTH release, while, surprisingly, it inhibited GH expression and release. Interestingly, these in vitro effects of obestatin on primate pituitary cultures were completely mimicked in mice treated in vivo with obestatin, suggesting that the effects of obestatin on pituitary cell function are conserved across species. Furthermore, obestatin treatment downregulated Pit-1 in both primate and mice pituitary cells, as well as mouse hypothalamic GHRH expression, which might contribute to the inhibitory effect of obestatin on GH expression and release observed in both species. Conversely, obestatin up-regulated expression of pituitary CRF-R1 in both models, and increased pituitary In2-ghrelin variant in mice, which may contribute to its stimulatory effects on POMC expression and ACTH release in both experimental models. Obestatin also down-regulated expression of somatostatin receptors 1 and 2 in both models, and also inhibited hypothalamic cortistatin in mice, thus reinforcing the evidence for its regulatory role on the GH and ACTH axes. Taken together, our results provide the first comprehensive experimental evidence to support a potential role of obestatin in the direct and opposite control of pituitary somatotrope and corticotrope function in mice and, most importantly, in a primate model.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details are unavailable.