Prolactin as an immuno-neuroendocrine integrator: linking immune homeostasis, hematopoietic dynamics and iron...

Prolactin (PRL) is traditionally recognized for its essential role in lactation and reproductive physiology. However, growing evidence establishes PRL as a pleiotropic immuno-neuroendocrine hormone with broad regulatory effects on innate and adaptive immunity, hematopoiesis, and inflammatory homeostasis. It exerts its actions through prolactin receptor that activate intracellular signaling cascades including JAK2/STAT5, MAPK/ERK, and PI3K/Akt pathways. These signaling networks influence lymphocyte survival, cytokine production, macrophage activation, dendritic cell maturation, and hematopoietic progenitor cell expansion. Notably, prolactin demonstrates context-dependent duality, exhibiting both pro-inflammatory and immunoregulatory functions. Dysregulated prolactin signaling has been implicated in autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. Additionally, prolactin interacts with the hypothalamic-pituitary-adrenal axis, dopaminergic pathways, and sex steroids, integrating neuroendocrine signals with immune responses. This review synthesizes mechanistic insights into prolactin biology, examines its hematopoietic and immunologic roles, critically evaluates current controversies, and discusses emerging therapeutic strategies targeting PRL signaling. Understanding context-specific actions of prolactin may enable precision-based immunomodulatory interventions.