Role of Endogenous Somatostatin and Cortistatin in Regulating Adrenal Gland Function
A. Moreno-Herrera1, J. Córdoba-Chacón1,2, M. Gahete1,2, A. Pozo-Salas1, L. de Lecea3, R. Kineman2, J. Castaño1 & R. Luque1
Neuroendocrine balance of the hypothalamo-pituitary-adrenal axis (HPA) is a critical component in the control of metabolic homeostasis, and its dysregulation can contribute to severe pathologies, like obesity, where the HPA is significantly altered at the central and systemic levels. Somatostatin and cortistatin have been shown to reduce circulating ACTH and glucocorticoid-levels in rodents and humans in vivo. However, to date, no studies have thoroughly investigated and compared the precise actions and potential physiological relevance of somatostatin/cortistatin at the adrenal gland level. Accordingly, here we studied the specific roles of endogenous somatostatin/cortistatin on the regulation of the adrenal gland by using somatostatin-knockout (KO) and cortistatin-KO mice and their wildtype-littermate controls, both under normal or obesity-conditions. Results revealed that circulating corticosterone levels were elevated in male/female somatostatin/cortistatin-KO as compared to normal controls. Similar results were observed in obesity conditions, although male plasma corticosterone levels were lower in obese cortistatin-KO. Interestingly, at the adrenal level, major gender- and genotype-dependent differences were found in the expression of key components potentially involved in glucocorticoid regulation. Specifically, MCR2 (main ACTH-receptor in adrenal gland) was not altered in cortistatin-KO while it was decreased in female somatostatin-KO under normal conditions, and increased in obese somatostatin-KO male mice. Interestingly, expression of 11β-hydroxysteroid-dehydrogenase and tyrosine-hydroxylase, two key markers associated with glucocorticoid synthesis were reduced in male somatostatin/cortistatin-KO mice under normal conditions, but were increased in female cortistatin-KO under normal conditions and in obese somatostatin-KO mice. These results, together with data showing major differences in somatostatin-, CRF-, IGFI- and leptin-receptors in the adrenal gland, reveal that endogenous somatostatin and cortistatin exert unique, gender-dependent actions in the control of adrenal function, which are tightly regulated in extreme metabolic-conditions (obesity), thereby inviting to investigate further the hitherto poorly explored relevance of both peptides in the (patho)physiological regulation of HPA axis.
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 unavailable.