{"doi":"10.20935/acadbiol7623","title":"VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmission","abstract":"Ventromedial hypothalamic nucleus (VMN) growth hormone-releasing hormone (Ghrh) neurotransmission governs counterregulatory hormone release. Recent studies document Ghrh control of hypoglycemia-sensitive counterregulatory neurotransmitter expression in dorsomedial VMN (VMNdm) Ghrh/steroidogenic factor-1 (SF-1) neurons. In this study, Ghrh receptor (Ghrh-R) gene silencing was implemented in vivo to determine if VMN Ghrh-R shapes counterregulation. Intra-VMN Ghrh-R siRNA augmented corticosterone secretion in vehicle or insulin-injected male rats, but this hormone was correspondingly refractory or inhibited in eu- versus hypoglycemic females. In each sex, gene knockdown up- or down-regulated baseline glucagon and growth hormone (GH) release, but hypoglycemia reversed the direction of Ghrh-R control of each hormone. Single-cell laser catapult-microdissected VMNdm Ghrh/SF-1 neuron multiplex qPCR analysis revealed contrary VMN Ghrh-R gene-silencing effects on eu- versus hypoglycemic SF-1 mRNA levels. In both sexes, Ghrh-R siRNA up-regulated mRNAs encoding counterregulation-repressive (γ-aminobutyric acid) or -enhancing (nitric oxide) transmitter protein markers, unrelated to plasma glycemic profiles. Ghrh-R regulation of Ghrh gene transcription was absent (euglycemic) or stimulatory (hypoglycemic) in females, and receptor control of glutaminase mRNA, a marker for the counterregulatory-augmenting neurochemical glutamate, was lost in hypoglycemic males. Ghrh-R gene silencing caused uniform up-regulation of 5'-AMP-activated protein kinase alpha-2 (AMPKα2) mRNA in each sex, independent of glucose status, but caused dissimilar changes in AMPKα1 transcription in eu- versus hypoglycemic females. The outcomes provide novel evidence that VMN Ghrh-R signaling imposes glucose-dependent control of counterregulatory hormone secretion and distinctive VMNdm neuron counterregulatory transmitter marker gene profiles. Data infer that this metabolic control may involve SF-1 (both sexes)- and AMPKα1 (female)-dependent mechanisms.","journal":"Academia Biology","year":2025,"id":552156,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"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":1260958,"name":"Rami Shrestha","orcid":"0000-0002-0191-8476","position":1,"is_corresponding":false},{"id":1283820,"name":"Sushma Katakam","orcid":null,"position":2,"is_corresponding":false},{"id":375108,"name":"Sagor C. Roy","orcid":null,"position":3,"is_corresponding":false},{"id":331582,"name":"Karen P. Briski","orcid":"0000-0002-7648-1395","position":4,"is_corresponding":false},{"id":1065018,"name":"Subash Sapkota","orcid":"0009-0004-4625-0037","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:54:33.203144Z","pmid":"40688570","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":[]}