{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:22:17Z","timestamp":1784859737409,"version":"3.55.0"},"reference-count":113,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Society of Endocrinology and Nutrition (SEEN)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prolactin (PRL) and growth hormone (GH) are peptide hormones that bind to the class 1 cytokine receptor superfamily, a highly conserved cell surface class of receptors. Both hormones control their own secretion via a negative autocrine loop in their own mammosomatotroph, lactotroph or somatotroph. In this regard, GH and PRL are regulated by similar signaling pathways involving cell growth and hormone secretion. Thus, GH and PRL dysregulation and pituitary neuroendocrine tumor (PitNET) development may have common pathogenic pathways. Based on cell linage, lactotroph and somatotroph PitNETs come from pituitary-specific POU-class homeodomain transcription factor (Pit-1). Mammosomatotroph and plurihormonal PitNETs are a unique subtype of PitNETs that arise from a single-cell population of Pit-1 lineage. In contrast, mixed somatotroph\u2013lactotroph PitNETs are composed of two distinct cell populations: somatotrophs and lactotrophs. Morphologic features that distinguish indolent PitNETs from locally aggressive ones are still unidentified, and no single prognostic parameter can predict tumor aggressiveness or treatment response. In this review, we aim to explore the latest research on lactotroph and somatotroph PitNETs, the molecular mechanisms involved in PRL and GH axis regulation and the signaling pathways involved in their aggressiveness, particularly focused on mammosomatotroph and mixed subtypes. Finally, we summarize epidemiological, clinical, and radiological features of these exceptional tumors. We aim to shed light, from basic to clinical settings, on new perspectives and scientific gaps in this field.<\/jats:p>","DOI":"10.3390\/ijms241814002","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T21:34:12Z","timestamp":1694554452000},"page":"14002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Prolactin and Growth Hormone Signaling and Interlink Focused on the Mammosomatotroph Paradigm: A Comprehensive Review of the Literature"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-0072","authenticated-orcid":false,"given":"Marta","family":"Araujo-Castro","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, Colmenar Viejo Street km 9, 28034 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica Ram\u00f3n y Cajal (IRYCIS), Colmenar Viejo Street km 9, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Marazuela","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Hospital Universitario La Princesa, 28006 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER GCV14\/ER\/12), Monforte de Lemos Avenue, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manel","family":"Puig-Domingo","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Department of Medicine, Germans Trias i Pujol Research Institute and Hospital, Universitat Aut\u00f2noma de Barcelona, 08916 Badalona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras CIBERER G747, Monforte de Lemos Avenue, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-4343","authenticated-orcid":false,"given":"Betina","family":"Biagetti","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Vall d\u2019Hebron University Hospital, Reference Networks (ERN) and Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron Avenue, 119, 08035 Barcelona, Spain"},{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute and CIBERDEM (ISCIII), Universidad Aut\u00f3noma de Barcelona, Avenida Can Dom\u00e8nech s\/n, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1152\/physrev.2000.80.4.1523","article-title":"Prolactin: Structure, Function, and Regulation of Secretion","volume":"80","author":"Freeman","year":"2000","journal-title":"Physiol. 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