About this Research Topic
Hyperprolactinemia is the main disease linked to PRL. It is in the vast majority of cases induced by benign tumors of the pituitary (prolactinomas). While high prolactin in lactation contributes to physiological suppression of fertility, inappropriate hyperprolactinemia leads to fertility disorders. Hyperprolactinemia is efficiently treated by dopamine agonists that negatively regulate pituitary PRL production and (near-) normalize PRL circulating levels. Besides this relatively well understood disease, dysregulation (up or down) of PRL or PRLR expression/signaling has been associated with various other pathologies, e.g. cancers, immune, metabolic, or behavioral disorders.
However, the actual functional contribution of PRL pathway alterations to the etiology and/or progression of disease - in other words, is PRL a cause or a consequence of the disease? – is not always very clear. Systemic and tissue-specific alteration of PRL or PRLR expression in cell/animal models provided mechanistic evidence on the actual effects of PRLR signaling in these pathologies. However, the disappointing results of the few clinical trials involving anti-PRLR molecules challenged not only the therapeutic efficacy of these new drugs, but also, and perhaps even more, the relevance of the clinical indications mainly based on preclinical models.
A possible reason for this could be that PRL, in pathology like in physiology, may contribute to, more than act as a real driver of, the many diseases referred to as "PRL-related". In addition, PRL is a versatile hormone that exerts a variety of actions (proliferation/anti-apoptosis, differentiation/secretion, etc.) that could ultimately result in promoting versus protective effects in diseases depending on confounding factors that remain to be identified. A typical example of such functional duality is breast cancer, in which the actual role of PRL is widely debated. Similarly, metabolic actions of prolactin suggest that either too much or too little might cause problems, with optimal function a finely tuned balance associated with the “just right” level of hormone.
In this complex landscape, the goal of this Research Topic is to overview the most recent data in the field to help better define pathologies in which PRL appears to exert promoting versus protective effects. As the ultimate goal of these studies is to pave the way towards the use of PRLR-targeting molecules in the clinics, the most recent advances in the development of new compounds or therapeutic strategies (molecule repositioning) is also of interest.
Keywords: Prolactin, PRLR-Targeting Molecules
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