{"doi":"10.1073/pnas.94.25.14132","title":"Multi-responsiveness of single anterior pituitary cells to hypothalamic-releasing hormones: A cellular basis for paradoxical secretion","abstract":"<jats:p>\n            The classic view for hypothalamic regulation of anterior pituitary (AP) hormone secretion holds that release of each AP hormone is controlled specifically by a corresponding hypothalamic-releasing hormone (HRH). In this scenario, binding of a given HRH (thyrotropin-, growth hormone-, corticotropin-, and luteinizing hormone-releasing hormones) to specific receptors in its target cell increases the concentration of cytosolic Ca\n            <jats:sup>2+</jats:sup>\n            ([Ca\n            <jats:sup>2+</jats:sup>\n            ]\n            <jats:sub>i</jats:sub>\n            ), thereby selectively stimulating the release of the appropriate hormone. However, “paradoxical” responses of AP cells to the four well-established HRHs have been observed repeatedly with both\n            <jats:italic>in vivo</jats:italic>\n            and\n            <jats:italic>in vitro</jats:italic>\n            systems, raising the possibility of functional overlap between the different AP cell types. To explore this possibility, we evaluated the effects of HRHs on [Ca\n            <jats:sup>2+</jats:sup>\n            ]\n            <jats:sub>i</jats:sub>\n            in single AP cells identified immunocytochemically by the hormone they stored. We found that each of the five major AP cell types contained discrete subpopulations that were able to respond to several HRHs. The relative abundance of these multi-responsive cells was 59% for lactotropes, 33% for thyrotropes, and in the range of 47–55% for gonadotropes, corticotropes, and somatotropes. Analysis of prolactin release from single living cells revealed that each of the four HRHs tested were able to induce hormone release from a discrete lactotrope subpopulation, the size of which corresponded closely to that in which [Ca\n            <jats:sup>2+</jats:sup>\n            ]\n            <jats:sub>i</jats:sub>\n            changes were induced by the same secretagogues. When viewed as a whole, our diverse functional measurements of multi-responsiveness suggest that hypothalamic control of pituitary function is more complicated than previously envisioned. Moreover, they provide a cellular basis for the so-called “paradoxical” behavior of pituitary cells to hypothalamic hypophysiotropic agents.\n          </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":1997,"id":26442,"datarank":3.621041108339677,"base_score":4.356708826689592,"endowment":4.356708826689592,"self_citation_contribution":0.6535063240034389,"citation_network_contribution":2.9675347843362383,"self_endowment_contribution":0.6535063240034389,"citer_contribution":2.9675347843362383,"corpus_percentile":null,"corpus_rank":null,"citation_count":77,"citer_count":58,"citers_with_citation_signal":50,"citers_with_endowment":50,"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":152955,"name":"Lucía Núñez","orcid":null,"position":1,"is_corresponding":false},{"id":152956,"name":"L. Stephen Frawley","orcid":null,"position":2,"is_corresponding":false},{"id":150028,"name":"Javier García-Sancho","orcid":null,"position":3,"is_corresponding":false},{"id":152957,"name":"Ana Sánchez","orcid":null,"position":4,"is_corresponding":false},{"id":152954,"name":"Carlos Villalobos","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.356708826689592,"endowment":4.356708826689592,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9391165","pmcid":null,"openalex_id":"https://openalex.org/W2147017380","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK38251","title":null}],"total_grants":1,"fwci":2.5031,"citation_percentile":0.89520958,"influential_citations":4,"citation_trend":[{"year":2012,"count":1},{"year":2014,"count":1},{"year":2015,"count":1},{"year":2016,"count":4},{"year":2017,"count":1},{"year":2018,"count":4},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":3},{"year":2022,"count":2},{"year":2024,"count":1},{"year":2026,"count":1}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://europepmc.org/articles/pmc28445?pdf=render","host_type":"GREEN"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.94.25.14132","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.94.25.14132","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9391165","host_type":"repository"},{"url":"http://hdl.handle.net/10261/71865","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/28445","host_type":"repository"},{"url":"http://uvadoc.uva.es/handle/10324/45077","host_type":"repository"}],"fields_of_study":["Stress Responses and Cortisol","Hypothalamic control of reproductive hormones","Regulation of Appetite and Obesity","Medicine","Biology","Animals","Calcium","Corticotropin-Releasing Hormone","Gonadotropin-Releasing Hormone","Hypothalamic Hormones","Immunohistochemistry","In Vitro Techniques","Male","Models, Neurological","Pituitary Gland, Anterior","Pituitary Hormones, Anterior","Prolactin","Rats","Rats, Wistar","Thyrotropin-Releasing Hormone"],"mesh_terms":["Animals","Calcium","Corticotropin-Releasing Hormone","Hypothalamic Hormones","Immunohistochemistry","Gonadotropin-Releasing Hormone","Male","Models, Neurological","Pituitary Gland, Anterior","Pituitary Hormones, Anterior","Prolactin","Thyrotropin-Releasing Hormone","Rats, Wistar","Rats","In Vitro Techniques"],"keywords":["Gonadotropic cell","Somatotropic cell","Corticotropic cell","Thyrotropic cell","Internal medicine","Endocrinology","Anterior pituitary","Prolactin","Hormone","Prolactin cell","Hypothalamic Hormones","Luteinizing hormone","Biology","Hypothalamus","Receptor","Endocrine gland","Thyrotropin-releasing hormone","Thyrotropin-releasing hormone receptor","Pituitary gland","Hormone receptor","Pituitary hormones","Medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T14:20:52.603688Z","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":[]}