Prolactin: The new biology of an old hormone

Prolactin (PRL) is a paradoxical hormone. Historically known as the pituitary hormone of lactation, it has had attributed to it more than 300 separate actions, which can be correlated to the quasi-ubiquitous distribution of its receptor. Meanwhile, PRL-related knockout models have mainly highlighted its irreplaceable role in functions of lactation and reproduction, which suggests that most of its other reported target tissues are presumably modulated by, rather than strictly dependent on, PRL. The multiplicity of PRL actions in animals is in direct opposition to the paucity of arguments that suggest its involvement in human pathophysiology other than effects on reproduction. Although many experimental data argue for a role of PRL in the progression of some tumors, such as breast and prostate cancers, drugs lowering circulating PRL levels are ineffective. This observation opens new avenues for research into the understanding of whether local production of PRL is involved in tumor growth and, if so, how extrapituitary PRL synthesis is regulated. Finally, the physiological relevance of PRL variants, such as the antiangiogenic 16K-like PRL fragments, needs to be elucidated. This review is aimed at critically discussing how these recent findings have renewed the manner in which PRL should be considered as a multifunctional hormone.