{"doi":"10.1210/en.2016-1195","title":"Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice","abstract":"<jats:p>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.</jats:p>","journal":"Endocrinology","year":2016,"id":46571,"datarank":0.5984231964172981,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.22568719894909794,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.22568719894909794,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":4,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":215808,"name":"Manuel D. Gahete","orcid":null,"position":1,"is_corresponding":false},{"id":215809,"name":"Ana I. Pozo-Salas","orcid":null,"position":2,"is_corresponding":false},{"id":198438,"name":"Luis de Lecea","orcid":null,"position":3,"is_corresponding":false},{"id":215810,"name":"Justo P. Castaño","orcid":null,"position":4,"is_corresponding":false},{"id":215811,"name":"Raúl M. Luque","orcid":null,"position":5,"is_corresponding":false},{"id":215807,"name":"José Cordoba-Chacón","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice","abstract":"<jats:p>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.</jats:p>","is_dataset_classified":null,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27175972","pmcid":null,"openalex_id":"https://openalex.org/W2391409986","authors":[],"funders":[],"total_grants":0,"fwci":1.6674,"citation_percentile":0.84381517,"influential_citations":0,"citation_trend":[{"year":2016,"count":3},{"year":2017,"count":2},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2022,"count":2},{"year":2025,"count":1}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://academic.oup.com/endo/article-pdf/157/7/2810/8995582/endo2810.pdf","host_type":"repository"},{"url":"https://academic.oup.com/endo/article-pdf/157/7/2810/8995582/endo2810.pdf","host_type":"repository"},{"url":"http://academic.oup.com/endo/article-pdf/157/7/2810/8995582/endo2810.pdf","host_type":"publisher"},{"url":"http://hdl.handle.net/10668/10078","host_type":"repository"},{"url":"https://doi.org/10.1210/en.2016-1195","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27175972","host_type":"repository"}],"fields_of_study":["Growth Hormone and Insulin-like Growth Factors","Regulation of Appetite and Obesity","Pituitary Gland Disorders and Treatments","Adrenocorticotropic Hormone","Animals","Blood Glucose","Cells, Cultured","Corticosterone","Fasting","Female","Ghrelin","Growth Hormone","Insulin","Leptin","Male","Mice","Mice, Knockout","Neuropeptides","Pituitary Gland","Sex Factors","Stress, Physiological","Stress, Psychological"],"mesh_terms":["Adrenocorticotropic Hormone","Animals","Blood Glucose","Cells, Cultured","Corticosterone","Fasting","Female","Insulin","Male","Neuropeptides","Pituitary Gland","Sex Factors","Growth Hormone","Stress, Physiological","Stress, Psychological","Mice, Knockout","Leptin","Mice","Ghrelin"],"keywords":["Internal medicine","Endocrinology","Corticosterone","Ghrelin","Somatotropic cell","Proopiomelanocortin","Biology","Somatostatin","Pituitary gland","Anterior pituitary","Hypothalamus","Hormone","Medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-11T01:43:06.973840Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}