{"doi":"10.1210/endocr/bqaf106","title":"RFRP Neurons Are Required for Acute Stress-induced Suppression of the Estrogen-stimulated LH Surge in Female Mice","abstract":"The association between perceived stress and reproductive dysfunction is known, yet the underlying mechanisms remain incompletely determined. We previously demonstrated that RF-amide related (RFRP) peptide 3-expressing neurons, putative inhibitors of the central regulation of fertility, are required for both acute restraint stress- and glucocorticoid-induced suppression of LH pulsatility in female mice. The present study complemented this by testing the role of RFRP neurons in the stress-induced suppression of the estrogen-induced preovulatory-like LH surge. We first established a reliable model of acute restraint stress in mice that stimulates glucocorticoid secretion, suppresses a late afternoon estrogen-induced LH surge, and inhibits corresponding kisspeptin neuronal activation in the anteroventral periventricular brain region. Two hours of restraint stress initiated 2 to 6 hours prior to lights off met these criteria. We then ablated RFRP neurons in adult female mice by expressing a diphtheria toxin receptor specifically in these cells and exposing them to diphtheria toxin. RFRP neuron-ablated and control mice that were ovariectomized and estrogen-treated were exposed to the acute, mid-afternoon restraint stress protocol and assessed for their peak LH concentrations several hours later at the expected time of the LH surge. Control mice exhibited stress-induced suppression of the LH surge, as expected, whereas RFRP-ablated mice did not. No differences in peak LH concentrations were observed between nonstressed controls and stressed RFRP-ablated mice. These data suggest that acute psychosocial stress occurring several hours prior to preovulatory LH surge induction invokes RFRP neuron-mediated blockade of the surge. The neural circuitry involved remains to be fully characterized.","journal":"Endocrinology","year":2025,"id":533861,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1416483,"name":"Shaun M Stowe","orcid":null,"position":1,"is_corresponding":false},{"id":1416039,"name":"India L Sawyer","orcid":"0000-0002-4803-0116","position":2,"is_corresponding":false},{"id":1416040,"name":"Caroline Decourt","orcid":"0000-0002-2181-0622","position":3,"is_corresponding":false},{"id":1416484,"name":"Frank W. Lee","orcid":null,"position":4,"is_corresponding":false},{"id":286313,"name":"Alexander S. Kauffman","orcid":"0000-0001-8631-6097","position":5,"is_corresponding":false},{"id":1036319,"name":"Greg M. Anderson","orcid":"0000-0002-6747-8047","position":6,"is_corresponding":false},{"id":1416038,"name":"Maggie C. Evans","orcid":"0000-0003-4102-7771","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:51:43.451278Z","pmid":"40488302","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":[]}