Endocrine Abstracts

Prolactin was discovered 80 years ago. It is currently viewed by clinical endocrinologists as a hormone of pituitary origin, whose production is negatively controlled by dopamine, whose biological actions relate exclusively to lactation and reproductive functions, for which any genetic disorder is yet to be identified, and whose unique associated pathology is hyperprolactinemia, which is efficiently cured using dopamine agonists. Although there is no debate about the relevance of these features, experimental and clinical studies performed during the past decade have considerably widened our perception of prolactin biology: i) in addition to the endocrine (circulating) hormone, locally-produced prolactin has been documented in various human tissues such as the mammary gland and the prostate, where it acts via autocrine/paracrine mechanisms, ii) there is increasing evidence supporting the role of prolactin in human breast and prostate tumorogenesis, especially when it is locally-produced, iii) we recently reported the first gain-of-function variant of the prolactin receptor, that was to date identified in patients presenting with breast tumors (benign or cancer), iv) we have engineered human prolactin variants acting as pure competitive antagonists of the prolactin receptor, and we have demonstrated their ability to down-regulate the actions triggered by local prolactin as well as by the constitutively active receptor variant in experimental models; these compounds thus represent a novel class of molecules of therapeutic interest as potential alternative to dopamine agonists. These novel aspects of prolactin biology will be presented, with major focus on experimental models highlighting its effects on tumor growth.