{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProlactin (PRL) is a multifunctional hormone with a pivotal role in reproduction and developmental biology. In the mammary gland, PRL stimulates cell growth and differentiation by upregulating cyclin D1 through the Jak2/STAT5 pathway, and autocrine production of PRL in breast epithelial cells further enhances estrogen responsiveness and receptor expression. In the skin and scalp, PRL is locally produced by hair follicles, where its actions are linked to the inhibition of hair shaft elongation and acceleration of catagen entry. In the human endometrium, PRL is a well‐established marker of decidualization, where its expression is tightly regulated by cooperative transcription factor networks. Moreover, PRL influences parental behavior by modulating aspects of father–infant play dynamics, while dysregulated PRL production in reproductive tissues can contribute to neoplastic transformation in ovarian and endometrial cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its reproductive and developmental roles, PRL exerts critical influences on cardiovascular and metabolic physiology. Under conditions of cardiac stress such as postpartum cardiomyopathy, proteolytic cleavage of full‐length PRL yields a 16‐kDa fragment with antiangiogenic and proapoptotic properties that disrupt the cardiac capillary network and impair myocardial function. Similar proteolytic processing, also observed in human tissues, generates bioactive PRL fragments that may act to constrain angiogenesis. In adipose tissue, PRL directly decreases lipoprotein lipase activity via its receptor, thereby modulating lipid metabolism during lactation. Elevated circulating PRL has further been linked to increased arterial blood pressure and aortic stiffness in early menopause, while recent studies suggest that altered PRL signaling may also influence the development of non‐alcoholic fatty liver disease and liver inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe biological activity of PRL is mediated by its receptor and the downstream signaling cascades it initiates. Structural analyses of human PRL and its receptor have revealed conserved ligand–receptor interaction motifs that activate classical pathways such as STAT5, while altered tissue microenvironments (for example, increased extracellular matrix stiffness) can shift PRL signaling from physiological to protumorigenic outcomes via SRC/FAK and ERK1/2 activation. In breast cancer cells, PRL signaling intersects with intracellular regulators by inducing suppressors such as SOCS3 and downregulating factors like BCL6, thereby modulating cell proliferation and differentiation. In addition, PRL acts as an immunomodulator, serving as a costimulatory factor for lymphocyte proliferation and survival. Insights into receptor–ligand dynamics have further paved the way for the development of PRL receptor antagonists, which may have therapeutic potential in malignancy and other PRL‐related disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jennifer L Brockman, Matthew D Schroeder, Linda A Schuler "}, {"type": "b", "children": [{"type": "t", "text": "PRL activates the cyclin D1 promoter via the Jak2/Stat pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/mend.16.4.0817"}], "href": "https://doi.org/10.1210/mend.16.4.0817"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11923474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11923474"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kerstin Foitzik, Karoline Krause, Franziska Conrad, et al. 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