Cordoba-Chacon, JoseGahete, Manuel DPozo-Salas, Ana Ide Lecea, LuisCastaño, Justo PLuque, Raul M2023-01-252023-01-252016-05-09Cordoba-Chacón J, Gahete MD, Pozo-Salas AI, de Lecea L, Castaño JP, Luque RM. Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice. Endocrinology. 2016 Jul;157(7):2810-23http://hdl.handle.net/10668/10078Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting.enAdrenocorticotropic hormoneAnimalsBlood glucoseCells, culturedCorticosteroneFastingFemaleGhrelinGrowth hormoneInsulinLeptinMaleMiceMice, knockoutNeuropeptidesPituitary glandSex factorsStress, physiologicalresearch article27175972open accessAyunoEstrés fisiológicoFactores sexualesGhrelinaHipófisisHormona del crecimientoInsulinaLeptinaNeuropéptidos10.1210/en.2016-11951945-7170https://academic.oup.com/endo/article-pdf/157/7/2810/8995582/endo2810.pdf