{"doi":"10.1016/j.celrep.2022.111509","title":"Stress-induced glucocorticoid desensitizes adrenoreceptors to gate the neuroendocrine response to somatic stress in male mice","abstract":"Noradrenergic afferents to hypothalamic corticotropin releasing hormone (CRH) neurons provide a major excitatory drive to the hypothalamic-pituitary-adrenal (HPA) axis via α1 adrenoreceptor activation. Noradrenergic afferents are recruited preferentially by somatic, rather than psychological, stress stimuli. Stress-induced glucocorticoids feed back onto the hypothalamus to negatively regulate the HPA axis, providing a critical autoregulatory constraint that prevents glucocorticoid overexposure and neuropathology. Whether negative feedback mechanisms target stress modality-specific HPA activation is not known. Here, we describe a desensitization of the α1 adrenoreceptor activation of the HPA axis following acute stress in male mice that is mediated by rapid glucocorticoid regulation of adrenoreceptor trafficking in CRH neurons. Glucocorticoid-induced α1 receptor trafficking desensitizes the HPA axis to a somatic but not a psychological stressor. Our findings demonstrate a rapid glucocorticoid suppression of adrenergic signaling in CRH neurons that is specific to somatic stress activation, and they reveal a rapid, stress modality-selective glucocorticoid negative feedback mechanism.","journal":"Cell Reports","year":2022,"id":252140,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":566195,"name":"Chun Chen","orcid":"0000-0002-6957-0103","position":1,"is_corresponding":false},{"id":566749,"name":"Grant L. Weiss","orcid":null,"position":2,"is_corresponding":false},{"id":566196,"name":"Xin Fu","orcid":"0009-0001-7478-0244","position":3,"is_corresponding":false},{"id":564899,"name":"Claire E. Stelly","orcid":"0000-0003-4635-4560","position":4,"is_corresponding":false},{"id":420182,"name":"Brook L.W. Sweeten","orcid":"0000-0002-8280-7435","position":5,"is_corresponding":false},{"id":335008,"name":"Parker S Tirrell","orcid":"0000-0002-9459-7025","position":6,"is_corresponding":false},{"id":896107,"name":"India Pursell","orcid":"0000-0002-7207-3589","position":7,"is_corresponding":false},{"id":566197,"name":"Carly R. Stevens","orcid":"0000-0002-8322-1030","position":8,"is_corresponding":false},{"id":566750,"name":"Marc O. Fisher","orcid":null,"position":9,"is_corresponding":false},{"id":566751,"name":"John C. Begley","orcid":null,"position":10,"is_corresponding":false},{"id":566198,"name":"Laura M. Harrison","orcid":"0000-0003-4440-7753","position":11,"is_corresponding":false},{"id":566199,"name":"Jeffrey G. Tasker","orcid":"0000-0003-1977-4199","position":12,"is_corresponding":false},{"id":566194,"name":"Zhiying Jiang","orcid":"0000-0002-3838-2791","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T00:24:46.226372Z","pmid":"36261014","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":[]}