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Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice.
- Source :
-
Endocrinology [Endocrinology] 2016 Jul; Vol. 157 (7), pp. 2810-23. Date of Electronic Publication: 2016 May 13. - Publication Year :
- 2016
-
Abstract
- Cortistatin (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.
- Subjects :
- Adrenocorticotropic Hormone blood
Animals
Blood Glucose metabolism
Cells, Cultured
Corticosterone blood
Female
Ghrelin blood
Growth Hormone blood
Insulin blood
Leptin blood
Male
Mice
Mice, Knockout
Neuropeptides genetics
Pituitary Gland cytology
Pituitary Gland metabolism
Sex Factors
Fasting metabolism
Neuropeptides metabolism
Stress, Physiological physiology
Stress, Psychological metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 157
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 27175972
- Full Text :
- https://doi.org/10.1210/en.2016-1195