Mechanisms of biological action of prolactin and pathophysiological aspects of hyperprolactinemia

This review summarizes current data on the polymorphic roles of prolactin (PRL) and the pathophysiological consequences of hyperprolactinemia (HPRL). It examines both the classical functions of PRL (lactotropic and reproductive) and its systemic effects on the organism. Particular attention is paid to the association of HPRL with reproductive, metabolic, and immune disorders, as well as oncogenesis. Aim of the study was to summarize current data on the molecular organization, regulation of secretion, and diverse effects of prolactin (PRL), and to evaluate the pathophysiological contribution of hyperprolactinemia to the development of a wide spectrum of disorders. Material and methods. An analysis of scientific publications from 1928 to 2025 was conducted using the PubMed, Google Scholar, and eLibrary databases. Results. PRL is a 23-kDa polypeptide hormone secreted primarily by the lactotrophs of the anterior pituitary gland, as well as by various peripheral tissues. PRL mediates its effects by binding to a specific transmembrane receptor, activating multiple signaling pathways, with the JAK2/Stat5 cascade considered the primary one. Alongside the main isoform, a 16K PRL (vasoinhibin) exists — an N-terminal fragment of the hormone possessing its own biological activity. This review systematizes current knowledge on the molecular organization, regulation of secretion, and diverse physiological functions of PRL. The involvement of PRL in maintaining metabolic homeostasis, regulating reproductive functions, modulating immune responses, and contributing to the development of inflammatory and autoimmune processes, as well as its role in oncogenesis, collectively underscores the significant impact of hyperprolactinemia (HPRL) in the pathogenesis of a wide spectrum of disorders. Conclusions. PRL has evolved from a regulator of reproduction to a key modulator of systemic homeostasis. A pathological increase in its level leads to systemic dysregulation of homeostatic mechanisms, which underlies reproductive, metabolic, immune disorders and oncological processes. Understanding the dual nature of PRL, the balance of concentrations of which determines the transition from physiology to pathology, opens up prospects for the development of new therapeutic strategies.