Time for a New Perspective on Prolactin in Metabolism

The longstanding notion of PRL being only diabetogenic is incorrect. Recent experimental and clinical studies show that PRL helps maintain a healthy metabolism. The beneficial effects of PRL occur at high values within normal circulating levels and above the conventional hyperprolactinemia threshold (25 μg/l). By contrast, low PRL values are associated with metabolic disease. PRL levels between 25 μg/l and 100 μg/l, conventionally defined as hyperprolactinemia, occur physiologically and are proposed to be defined as homeostatic functionally increased transient prolactinemia (HomeoFIT-PRL), since they may contribute to maintaining and promoting metabolic homeostasis. Drugs elevating systemic PRL are promising therapeutics for obesity-derived metabolic alterations, such as T2D. 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. 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. adaptation of metabolic functions to sustain a challenged or demanding physiological state. A typical example would be the metabolic changes occurring in the mother to sustain pregnancy and lactation. prolactinemia in the range between 25 μg/l and up to ~100 μg/l necessary for maintaining metabolic homeostasis. It can also occur in metabolically demanding physiological situations, such as stress, hypoglycemia, and exercise, and is not associated with any pathophysiological cause. a benign tumor of the pituitary gland that produces excessive amounts of PRL. Symptoms of prolactinoma may include infertility, osteoporosis, reduced libido, low levels of sex hormones, galactorrhoea (milk production without pregnancy and lactation), and amenorrhea (absence of menstruation).