Time for a New Perspective on Prolactin in Metabolism

The pituitary hormone prolactin (PRL) regulates a variety of functions beyond reproduction. The association between physiological (pregnancy) and pathological (prolactinoma) hyperprolactinemia and metabolic alterations led to the concept of this hormone being diabetogenic. However, large cohort clinical studies have recently shown that low circulating PRL levels are associated with metabolic disease and represent a risk factor for type 2 diabetes (T2D), whereas high PRL levels are beneficial. Moreover, PRL acts on the pancreas, liver, adipose tissue, and hypothalamus to maintain and promote metabolic homeostasis. By integrating basic and clinical evidence, we hypothesize that upregulation of PRL levels is a mechanism to maintain metabolic homeostasis and, thus, propose that the range of PRL levels considered physiological should be expanded to higher values.