3626fc0a128f5b6cd6bf31a90fcf6413 ijms-24-14002.pdf 77a6dea1eedb8503370f3b0f9ebc5a4f0fdeefc3 ijms-24-14002.pdf eeece2d3c84bd1fd286e77694264f6001fbe7bb2e21cf81df290428fdb344551 ijms-24-14002.pdf Title: Prolactin and Growth Hormone Signaling and Interlink Focused on the Mammosomatotroph Paradigm: A Comprehensive Review of the Literature Subject: 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–lactotroph 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. Keywords: acromegaly; prolactin; pituitary neuroendocrine tumors; growth hormone; mammosomatotroph; prolactin receptor; dopamine receptor; somatostatin receptor; plurihormonal tumors Author: Marta Araujo-Castro, Mónica Marazuela, Manel Puig-Domingo and Betina Biagetti Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Sep 12 12:52:06 2023 CEST ModDate: Tue Sep 12 12:55:20 2023 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2326361 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SOZKOC+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 JODICL+VnURWPalladioL Type 1 Custom yes yes no 15 0 EPLBED+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 KTQFLB+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 RYFQLW+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 46 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 QDCWHF+EURM10 Type 1 Builtin yes yes no 74 0 IDJPIE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 87 0 IDJPIF+PalatinoLinotype CID TrueType Identity-H yes yes yes 90 0 IDJPIG+PalatinoLinotype TrueType WinAnsi yes yes no 96 0 IDJPJI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 99 0 IDKAEH+PalatinoLinotype TrueType MacRoman yes yes no 102 0 IDJPIE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 121 0 IDJPIF+PalatinoLinotype CID TrueType Identity-H yes yes yes 124 0 IDJPIG+PalatinoLinotype TrueType WinAnsi yes yes no 130 0 IDJPJI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 133 0 IDKAEH+PalatinoLinotype TrueType MacRoman yes yes no 136 0 SSJMKU+CMSY10 Type 1 Builtin yes yes no 150 0 IDJPIE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 164 0 IDJPIF+PalatinoLinotype CID TrueType Identity-H yes yes yes 167 0 IDJPIG+PalatinoLinotype TrueType WinAnsi yes yes no 173 0 IDJPJI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 176 0 IDKAEH+PalatinoLinotype TrueType MacRoman yes yes no 179 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-07-02 04:13:04 CEST RepresentationInformation: ijms-24-14002.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-07-01 18:01:01 CEST Size: 2326361 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 632 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Methods Destination: section.2 Item: Title: Ontogeny and Cell Linage Destination: section.3 Item: Title: Prolactin and GH Receptor in the Mammosomatotroph Cell Destination: section.4 Item: Title: Dopamine Receptor Destination: section.5 Item: Title: GHRH Receptor and Ghrelin Receptor Destination: section.6 Item: Title: Somatostatin Receptors Destination: section.7 Item: Title: Classification of GH PRL-Secreting PitNETs Destination: section.8 Item: Title: Clinical Aspects and Outcomes of GH PRL PitNETs Destination: section.9 Children: Item: Title: Prevalence and Epidemiological Aspects Destination: subsection.9.1 Item: Title: Clinical and Hormonal Behavior Destination: subsection.9.2 Item: Title: Radiological Features Destination: subsection.9.3 Item: Title: Surgical and Medical Outcomes Destination: subsection.9.4 Item: Title: Future Directions and Conclusions Destination: section.10 Item: Title: References Destination: section.11 Info: Title: Prolactin and Growth Hormone Signaling and Interlink Focused on the Mammosomatotroph Paradigm: A Comprehensive Review of the Literature Author: Marta Araujo-Castro, Mónica Marazuela, Manel Puig-Domingo and Betina Biagetti Subject: 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 lactotroph 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. Keywords: acromegaly; prolactin; pituitary neuroendocrine tumors; growth hormone; mammosomatotroph; prolactin receptor; dopamine receptor; somatostatin receptor; plurihormonal tumors Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Sep 12 12:52:06 CEST 2023 ModDate: Tue Sep 12 12:55:20 CEST 2023 ID: 0xe7489ae9395dc6cbeb38eaff9d2ec22e, 0xe7489ae9395dc6cbeb38eaff9d2ec22e Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: EPLBED+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 150 FontDescriptor: FontName: EPLBED+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: SSJMKU+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: SSJMKU+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: KTQFLB+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: KTQFLB+URWPalladioL-Roma Flags: 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