{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:39Z","timestamp":1787028459211,"version":"build-2736575974"},"reference-count":96,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prolactinoma has the highest incidence rate among patients with functional pituitary tumours. Although mostly benign, there is a subgroup that can be aggressive. Some clinical, radiological and pathology features have been associated with a poor prognostic. Therefore, it can be considered as a group of heterogeneous tumours. The aim of this paper is to give an overview of the molecular pathways involved in the behaviour of prolactinoma in order to improve our approach and gain deeper insight into the better understanding of tumour development and its management. This is essential for identifying patients harbouring aggressive prolactinoma and to establish personalised therapeutics options.<\/jats:p>","DOI":"10.3390\/ijms222011247","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T22:52:47Z","timestamp":1634683967000},"page":"11247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Molecular Pathways in Prolactinomas: Translational and Therapeutic Implications"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-4343","authenticated-orcid":false,"given":"Betina","family":"Biagetti","sequence":"first","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron University Hospital and Vall d\u2019Hebron Research Institute (VHIR), Universidad Aut\u00f3noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-3096","authenticated-orcid":false,"given":"Rafael","family":"Sim\u00f2","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron University Hospital and Vall d\u2019Hebron Research Institute (VHIR), Universidad Aut\u00f3noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101290","DOI":"10.1016\/j.beem.2019.101290","article-title":"The Epidemiology, Diagnosis and Treatment of Prolactinomas: The Old and the New","volume":"33","author":"Chanson","year":"2019","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1159\/000497746","article-title":"Epidemiology and Management Challenges in Prolactinomas","volume":"109","author":"Vroonen","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1530\/EJE-17-0933","article-title":"ESE survey collaborators Treatment of Aggressive Pituitary Tumours and Carcinomas: Results of a European Society of Endocrinology (ESE) Survey 2016","volume":"178","author":"McCormack","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-17-0796","article-title":"European Society of Endocrinology Clinical Practice Guidelines for the Management of Aggressive Pituitary Tumours and Carcinomas","volume":"178","author":"Raverot","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s11102-016-0723-4","article-title":"Giant Prolactinomas Larger than 60 Mm in Size: A Cohort of Massive and Aggressive Prolactin-Secreting Pituitary Adenomas","volume":"19","author":"Shimon","year":"2016","journal-title":"Pituitary"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1210\/jc.2014-3670","article-title":"Macroprolactinomas in Children and Adolescents: Factors Associated with the Response to Treatment in 77 Patients","volume":"100","author":"Salenave","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","first-page":"2102","article-title":"Sex-Related Difference in the Growth of Prolactinomas: A Clinical and Proliferation Marker Study","volume":"82","author":"Delgrange","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gao, H., Wang, F., Lan, X., Li, C., Feng, J., Bai, J., Cao, L., Gui, S., Hong, L., and Zhang, Y. (2015). Lower PRDM2 Expression Is Associated with Dopamine-Agonist Resistance and Tumor Recurrence in Prolactinomas. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1267-0"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"R559","DOI":"10.1530\/ERC-18-0228","article-title":"Aggressive and Malignant Pituitary Tumours: State-of-the-Art","volume":"25","author":"Dworakowska","year":"2018","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s12022-017-9498-z","article-title":"Overview of the 2017 WHO Classification of Pituitary Tumors","volume":"28","author":"Mete","year":"2017","journal-title":"Endocr. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/s11102-017-0861-3","article-title":"Prognostic Factors of Regrowth in Nonfunctioning Pituitary Tumors","volume":"21","author":"Raverot","year":"2018","journal-title":"Pituitary"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s00701-005-0498-2","article-title":"Clinical and Histological Correlations in Prolactinomas, with Special Reference to Bromocriptine Resistance","volume":"147","author":"Delgrange","year":"2005","journal-title":"Acta Neurochir. (Wien)"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1159\/000499382","article-title":"Clinical, Pathological, and Molecular Factors of Aggressiveness in Lactotroph Tumours","volume":"109","author":"Trouillas","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1159\/000371806","article-title":"Aggressive Pituitary Tumors","volume":"101","author":"Chatzellis","year":"2015","journal-title":"Neuroendocrinology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"604644","DOI":"10.3389\/fendo.2021.604644","article-title":"How to Classify and Define Pituitary Tumors: Recent Advances and Current Controversies","volume":"12","author":"Dai","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_16","unstructured":"Ganapathy, M.K., and Tadi, P. (2021). Anatomy, Head and Neck, Pituitary Gland. StatPearls, StatPearls Publishing."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/BF00210884","article-title":"Effects of Brain and Mesenchyme upon the Cytogenesis of Rat Adenohypophysis in Vitro. I. Differentiation of Adrenocorticotropes","volume":"227","author":"Watanabe","year":"1982","journal-title":"Cell Tissue Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/346583a0","article-title":"Autoregulation of Pit-1 Gene Expression Mediated by Two Cis-Active Promoter Elements","volume":"346","author":"Chen","year":"1990","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00003.2011","article-title":"Cellular and Molecular Specificity of Pituitary Gland Physiology","volume":"92","author":"Renner","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_20","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. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9173","DOI":"10.1523\/JNEUROSCI.1471-16.2016","article-title":"Conditional Deletion of the Prolactin Receptor Reveals Functional Subpopulations of Dopamine Neurons in the Arcuate Nucleus of the Hypothalamus","volume":"36","author":"Brown","year":"2016","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1159\/000122683","article-title":"Plasma Luteinizing Hormone and Prolactin Levels and Hypothalamic Catecholamine Synthesis in Steroid-Treated Ovariectomized Rats","volume":"23","author":"Jimenez","year":"1977","journal-title":"Neuroendocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4791","DOI":"10.1096\/fj.201701111RR","article-title":"Autocrine Actions of Prolactin Contribute to the Regulation of Lactotroph Function in Vivo","volume":"32","author":"Bernard","year":"2018","journal-title":"FASEB J."},{"key":"ref_24","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., de Herder, W.W., Dhatariya, K., Dungan, K., Grossman, A., Hershman, J.M., and Hofland, J. (2000). Hyperprolactinemia. Endotext, MDText.com, Inc."},{"key":"ref_25","first-page":"929","article-title":"Pharmacological Causes of Hyperprolactinemia","volume":"3","author":"Torre","year":"2007","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1159\/000054331","article-title":"Selective Inhibition of Magnocellular Vasopressin Neurons by Hypoosmolality: Effect on Histamine- and Stress-Induced Secretion of Adrenocorticotropin and Prolactin","volume":"67","author":"Kjaer","year":"1998","journal-title":"Neuroendocrinology"},{"key":"ref_27","first-page":"189","article-title":"In GH3 Pituitary Cells, Acetylcholine and Vasoactive Intestinal Peptide Antagonistically Modulate Adenylate Cyclase, Cyclic AMP Content, and Prolactin Secretion","volume":"24","author":"Onali","year":"1983","journal-title":"Mol. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1097\/JCP.0b013e31820e4832","article-title":"Impact of Different Antidopaminergic Mechanisms on the Dopaminergic Control of Prolactin Secretion","volume":"31","author":"Schorn","year":"2011","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s11102-008-0106-6","article-title":"Drugs and Prolactin","volume":"11","author":"Molitch","year":"2008","journal-title":"Pituitary"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12888","DOI":"10.1111\/jne.12888","article-title":"Metabolic Functions of Prolactin: Physiological and Pathological Aspects","volume":"32","author":"Winne","year":"2020","journal-title":"J. Neuroendocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Borba, V.V., Zandman-Goddard, G., and Shoenfeld, Y. (2018). Prolactin and Autoimmunity. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00073"},{"key":"ref_32","first-page":"851","article-title":"Novel Evidence That Pituitary Sex Hormones Regulate Migration, Adhesion, and Proliferation of Embryonic Stem Cells and Teratocarcinoma Cells","volume":"39","author":"Sellers","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1210\/edrv.22.6.0451","article-title":"Dopamine as a Prolactin (PRL) Inhibitor","volume":"22","author":"Hnasko","year":"2001","journal-title":"Endocr. Rev."},{"key":"ref_34","unstructured":"Bhatia, A., Lenchner, J.R., and Saadabadi, A. (2021). Biochemistry, Dopamine Receptors. StatPearls, StatPearls Publishing."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.semcdb.2020.10.005","article-title":"Prolactin: A Hormone with Diverse Functions from Mammary Gland Development to Cancer Metastasis","volume":"114","author":"Govindrajan","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_36","first-page":"85","article-title":"The Prolactin Receptor: Diverse and Emerging Roles in Pathophysiology","volume":"2","author":"Gorvin","year":"2015","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1042\/bse0450109","article-title":"Systems Biology of JAK\/STAT Signalling","volume":"45","author":"Pfeifer","year":"2008","journal-title":"Essays Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ferraris, J., Z\u00e1rate, S., Jaita, G., Boutillon, F., Bernadet, M., Auffret, J., Seilicovich, A., Binart, N., Goffin, V., and Pisera, D. (2014). Prolactin Induces Apoptosis of Lactotropes in Female Rodents. PloS One, 9.","DOI":"10.1371\/journal.pone.0097383"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/978-3-319-12114-7_7","article-title":"Role of SRC Family Kinases in Prolactin Signaling","volume":"846","author":"Calcabrini","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1159\/000494975","article-title":"JAK2\/STAT5 Pathway Mediates Prolactin-Induced Apoptosis of Lactotropes","volume":"108","author":"Orrillo","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrc1974","article-title":"MTOR and Cancer: Insights into a Complex Relationship","volume":"6","author":"Sabatini","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1677\/ERC-09-0101","article-title":"Activation of RAF\/MEK\/ERK and PI3K\/AKT\/MTOR Pathways in Pituitary Adenomas and Their Effects on Downstream Effectors","volume":"16","author":"Dworakowska","year":"2009","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"R331","DOI":"10.1530\/ERC-14-0188","article-title":"The PI3K\/AKT\/MTOR Pathway in the Pathophysiology and Treatment of Pituitary Adenomas","volume":"21","author":"Monsalves","year":"2014","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1093\/hmg\/ddy396","article-title":"Association of Prolactin Receptor (PRLR) Variants with Prolactinomas","volume":"28","author":"Gorvin","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13045-020-00949-4","article-title":"The MAPK and AMPK Signalings: Interplay and Implication in Targeted Cancer Therapy","volume":"13","author":"Yuan","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1210\/me.2014-1168","article-title":"Persistent ERK\/MAPK Activation Promotes Lactotrope Differentiation and Diminishes Tumorigenic Phenotype","volume":"28","author":"Booth","year":"2014","journal-title":"Mol. Endocrinol. Baltim. Md"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0896-6273(00)80352-9","article-title":"Antiproliferative Role of Dopamine: Loss of D2 Receptors Causes Hormonal Dysfunction and Pituitary Hyperplasia","volume":"19","author":"Saiardi","year":"1997","journal-title":"Neuron"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000094308","article-title":"Dopaminergic D2 Receptor Knockout Mouse: An Animal Model of Prolactinoma","volume":"35","author":"Cristina","year":"2006","journal-title":"Front. Horm. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0896-6273(00)80353-0","article-title":"Anterior Pituitary Hypoplasia and Dwarfism in Mice Lacking the Dopamine Transporter","volume":"19","author":"Fumagalli","year":"1997","journal-title":"Neuron"},{"key":"ref_50","first-page":"568","article-title":"Normal Structural Dopamine Type 2 Receptor Gene in Prolactin-Secreting and Other Pituitary Tumors","volume":"78","author":"Friedman","year":"1994","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s11102-016-0776-4","article-title":"Cabergoline and Prolactinomas: Lack of Association between DRD2 Polymorphisms and Response to Treatment","volume":"20","author":"Bueno","year":"2017","journal-title":"Pituitary"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1172\/JCI0215912","article-title":"Lack of Prolactin Receptor Signaling in Mice Results in Lactotroph Proliferation and Prolactinomas by Dopamine-Dependent and -Independent Mechanisms","volume":"110","author":"Schuff","year":"2002","journal-title":"J. Clin. Invest."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1101\/gad.11.2.167","article-title":"Null Mutation of the Prolactin Receptor Gene Produces Multiple Reproductive Defects in the Mouse","volume":"11","author":"Ormandy","year":"1997","journal-title":"Genes Dev."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"\u0160o\u0161i\u0107-Jurjevi\u0107, B., Ajd\u017eanovi\u0107, V., Milji\u0107, D., Trifunovi\u0107, S., Filipovi\u0107, B., Stankovi\u0107, S., Bolevich, S., Jakovljevi\u0107, V., and Milo\u0161evi\u0107, V. (2020). Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens\u2014An Insight From Translational Studies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062024"},{"key":"ref_55","first-page":"174","article-title":"Expression of Estrogen Receptor \u03b1 and Growth Factors in Human Prolactinoma and Its Correlation with Clinical Features and Gender","volume":"35","author":"Lv","year":"2012","journal-title":"J. Endocrinol. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1530\/EJE-14-0990","article-title":"Expression of Estrogen Receptor Alpha Is Associated with Prolactin Pituitary Tumor Prognosis and Supports the Sex-Related Difference in Tumor Growth","volume":"172","author":"Delgrange","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s11102-020-01029-z","article-title":"Expression Patterns of ER\u03b166 and Its Novel Variant Isoform ER\u03b136 in Lactotroph Pituitary Adenomas and Associations with Clinicopathological Characteristics","volume":"23","author":"Mahboobifard","year":"2020","journal-title":"Pituitary"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"706","DOI":"10.3389\/fendo.2018.00706","article-title":"Sex-Related Differences in Lactotroph Tumor Aggressiveness Are Associated With a Specific Gene-Expression Signature and Genome Instability","volume":"9","author":"Wierinckx","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.7150\/ijms.51176","article-title":"Estrogen Receptor \u03b1\/Prolactin Receptor Bilateral Crosstalk Promotes Bromocriptine Resistance in Prolactinomas","volume":"17","author":"Xiao","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1172\/JCI119779","article-title":"Somatostatin Receptor (SSTR) Subtype-Selective Analogues Differentially Suppress in Vitro Growth Hormone and Prolactin in Human Pituitary Adenomas. Novel Potential Therapy for Functional Pituitary Tumors","volume":"100","author":"Shimon","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_61","first-page":"3268","article-title":"Quantitative and Functional Expression of Somatostatin Receptor Subtypes in Human Prolactinomas","volume":"84","author":"Jaquet","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"K21","DOI":"10.1530\/EJE-19-0279","article-title":"Excellent Response to Pasireotide Therapy in an Aggressive and Dopamine-Resistant Prolactinoma","volume":"181","author":"Coopmans","year":"2019","journal-title":"Eur. J. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ando.2018.07.013","article-title":"Pasireotide: A Potential Therapeutic Alternative for Resistant Prolactinoma","volume":"80","author":"Lasolle","year":"2019","journal-title":"Ann. Endocrinol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"dgaa040","DOI":"10.1210\/clinem\/dgaa040","article-title":"Significant Benefits of AIP Testing and Clinical Screening in Familial Isolated and Young-Onset Pituitary Tumors","volume":"105","author":"Marques","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s12020-021-02633-0","article-title":"The Clinical Aspects of Pituitary Tumour Genetics","volume":"71","author":"Korbonits","year":"2021","journal-title":"Endocrine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11102-015-0674-1","article-title":"Gene Expression in Prolactinomas: A Systematic Review","volume":"19","author":"Seltzer","year":"2016","journal-title":"Pituitary"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s12022-019-09587-0","article-title":"The Genomic Landscape of Sporadic Prolactinomas","volume":"30","author":"Wang","year":"2019","journal-title":"Endocr. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1038\/s41467-020-16052-8","article-title":"Somatic SF3B1 Hotspot Mutation in Prolactinomas","volume":"11","author":"Li","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nrc2271","article-title":"Roles of HMGA Proteins in Cancer","volume":"7","author":"Fusco","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1038\/sj.onc.1208501","article-title":"Transgenic Mice Overexpressing the Wild-Type Form of the HMGA1 Gene Develop Mixed Growth Hormone\/Prolactin Cell Pituitary Adenomas and Natural Killer Cell Lymphomas","volume":"24","author":"Fedele","year":"2005","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1038\/sj.onc.1205428","article-title":"Overexpression of the HMGA2 Gene in Transgenic Mice Leads to the Onset of Pituitary Adenomas","volume":"21","author":"Fedele","year":"2002","journal-title":"Oncogene"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1210\/jc.2009-1238","article-title":"Recurrence of Hyperprolactinemia after Withdrawal of Dopamine Agonists: Systematic Review and Meta-Analysis","volume":"95","author":"Dekkers","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e4558","DOI":"10.1210\/clinem\/dgaa652","article-title":"Predictors of the Response to Dopaminergic Therapy in Patients With Prolactinoma","volume":"105","author":"Hage","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Ma, Q., Su, J., Li, Y., Wang, J., Long, W., Luo, M., and Liu, Q. (2018). The Chance of Permanent Cure for Micro- and Macroprolactinomas, Medication or Surgery? A Systematic Review and Meta-Analysis. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00636"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.wneu.2015.10.090","article-title":"Cost-Effectiveness Analysis of Microscopic and Endoscopic Transsphenoidal Surgery Versus Medical Therapy in the Management of Microprolactinoma in the United States","volume":"87","author":"Jethwa","year":"2016","journal-title":"World Neurosurg."},{"key":"ref_76","first-page":"2247","article-title":"Macroprolactinoma Shrinkage during Cabergoline Treatment Is Greater in Naive Patients than in Patients Pretreated with Other Dopamine Agonists: A Prospective Study in 110 Patients","volume":"85","author":"Colao","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3109\/02688697.2012.714817","article-title":"Medically Treated Prolactin-Secreting Pituitary Adenomas: When Should We Operate?","volume":"27","author":"Vale","year":"2013","journal-title":"Br. J. Neurosurg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1530\/EJE-19-0753","article-title":"Prolactin \u22641 Ng\/ML Predicts Macroprolactinoma Reduction after Cabergoline Therapy","volume":"182","author":"Kim","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4721","DOI":"10.1210\/jc.2007-2758","article-title":"Prospective Study of High-Dose Cabergoline Treatment of Prolactinomas in 150 Patients","volume":"93","author":"Ono","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11102-005-5085-2","article-title":"Pharmacologic Resistance in Prolactinoma Patients","volume":"8","author":"Molitch","year":"2005","journal-title":"Pituitary"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3803\/EnM.2014.29.3.280","article-title":"Early Prediction of Long-Term Response to Cabergoline in Patients with Macroprolactinomas","volume":"29","author":"Lee","year":"2014","journal-title":"Endocrinol. Metab."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Biagetti, B., Sarria-Estrada, S., Ng-Wong, Y.K., Martinez-Saez, E., Caster\u00e0s, A., Cordero Asanza, E., Hernandez, I., Giralt-Arnaiz, M., and Sim\u00f3, R. (2021). Shrinkage by the Third Month Predicts Long-Term Response of Macroprolactinoma after Cabergoline. Eur. J. Endocrinol., EJE-21-0561.R2.","DOI":"10.1530\/endoabs.73.AEP490"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"19749","DOI":"10.1002\/jcb.29281","article-title":"Atiprimod Induce Apoptosis in Pituitary Adenoma: Endoplasmic Reticulum Stress and Autophagy Pathways","volume":"120","author":"Keceloglu","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Aydin, B., Arslan, S., Bayrakl\u0131, F., Karademir, B., and Arga, K.Y. (2021). MiRNA-Mediated Drug Repurposing Unveiled Potential Candidate Drugs for Prolactinoma Treatment. Neuroendocrinology.","DOI":"10.1159\/000515801"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1210\/jc.2018-02461","article-title":"Effect of Everolimus in Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas","volume":"104","author":"Zhang","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_86","first-page":"51","article-title":"Multimodal Non-Surgical Treatments of Aggressive Pituitary Tumors","volume":"12","author":"Lau","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ding, Q., Zhang, Y., Ma, L., Chen, Y., Wu, J., Zhang, H., and Wang, X. (2020). Inhibiting MAPK14 Showed Anti-Prolactinoma Effect. BMC Endocr. Disord., 20.","DOI":"10.1186\/s12902-020-00619-z"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1158\/1535-7163.MCT-09-1186","article-title":"Metformin in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug?","volume":"9","author":"Tanti","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6368","DOI":"10.1111\/jcmm.13963","article-title":"Metformin Inhibits Growth and Prolactin Secretion of Pituitary Prolactinoma Cells and Xenografts","volume":"22","author":"Gao","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Portari, L.H.C., Correa-Silva, S.R., and Abucham, J. (2021). PROLACTIN RESPONSE TO METFORMIN IN CABERGOLINE-RESISTANT PROLACTINOMAS: A PILOT STUDY. Neuroendocrinology.","DOI":"10.1159\/000514591"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1507\/endocrj.EJ13-0245","article-title":"Differences between Rat Strains in the Development of PRL-Secreting Pituitary Tumors with Long-Term Estrogen Treatment: In Vitro Insulin-like Growth Factor-1-Induced Lactotroph Proliferation and Gene Expression Are Affected in Wistar-Kyoto Rats with Low Estrogen-Susceptibility","volume":"60","author":"Mitsui","year":"2013","journal-title":"Endocr. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1093\/brain\/awy108","article-title":"The Occurrence of Benign Brain Tumours in Transgender Individuals during Cross-Sex Hormone Treatment","volume":"141","author":"Nota","year":"2018","journal-title":"Brain J. Neurol."},{"key":"ref_93","first-page":"646","article-title":"PROLACTIN LEVELS DO NOT RISE AMONG TRANSGENDER WOMEN TREATED WITH ESTRADIOL AND SPIRONOLACTONE","volume":"24","author":"Bisson","year":"2018","journal-title":"Endocr. Pract. Off. J. Am. Coll. Endocrinol. Am. Assoc. Clin. Endocrinol."},{"key":"ref_94","first-page":"684","article-title":"THE EFFECT OF RALOXIFENE ON SERUM PROLACTIN LEVEL IN PATIENTS WITH PROLACTINOMA","volume":"25","author":"Choudhary","year":"2019","journal-title":"Endocr. Pract. Off. J. Am. Coll. Endocrinol. Am. Assoc. Clin. Endocrinol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Turchini, J., Sioson, L., Clarkson, A., Sheen, A., and Gill, A.J. (2021). PD-L1 Is Preferentially Expressed in PIT-1 Positive Pituitary Neuroendocrine Tumours. Endocr. Pathol.","DOI":"10.1007\/s12022-021-09673-2"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1210\/jc.2010-1692","article-title":"Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline","volume":"96","author":"Melmed","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11247\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:17:31Z","timestamp":1760167051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,18]]},"references-count":96,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms222011247"],"URL":"https:\/\/doi.org\/10.3390\/ijms222011247","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,18]]}}}