Prolactin: The New Biology of an Old Hormone

Abstract

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.

Prolactin Is Not Required for the Development of Severe Chronic Experimental Autoimmune Encephalomyelitis

“…Prolactin (PRL) is a 199-aa peptide hormone mainly secreted by lactotrophic cells of the anterior pituitary gland and by other sources including immune cells (8). The best established functions of PRL are related to mammary gland development and regulation of lactation and female reproduction (9). Mean PRL serum levels are slightly but significantly higher in women (∼2-20 mg/l) than in men (∼2-10 mg/l) (10).…”

“…However, stimulation of D2 dopaminergic receptors on immune cells can modulate their functions, and BCR has been shown to directly suppress human T cell proliferation independently of PRL (23). Moreover, BCR might not allow a complete depletion of PRL, as other extrapituitary sites of PRL secretion have been suggested (9). Given these limitations, a clear indication about the role of PRL in MS and EAE is still lacking.…”

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

“…It is also produced locally by multiple extrapituitary sites, including the mammary epithelium, placenta, uterus, bone, brain and immune system, and can act in an autocrine/ paracrine manner (Ben-Jonathan et al, 1996;Freeman et al, 2000). PRL stimulates normal mammary growth, development and lactation, but also affects other reproductive aspects,such as osmoregulation, stress and behavior (Horseman, 1999;Rui, 2000;Hovey et al, 2001;Goffin et al, 2002;Grimm et al, 2002). Although controversial, the contribution of PRL to the pathogenesis and progression of human breast cancer is increasingly appreciated (Hankinson et al, 1999;Vonderhaar, 1999;Llovera et al, 2000b;Ben-Jonathan et al, 2002;Clevenger et al, 2003).…”

La prolactine et son fragment 16 kDa dans les tissus de mammifères

“…Celle-ci agit sur les régions promotrices de gènes cibles, les gènes codant pour des protéines du lait par exemple (Figure 2A-C), ou contrôle les activités de prolifération et de croissance ( Figure 2E) [2]. Dans la glande mammaire, les effets de la PRL sur le transport des protéines sécrétées par les cellules épithéliales mammaires [19] mettent en jeu l'activation d'une cascade d'activation de la phospholipase A2 et la libération d'acide arachidonique [20] (Figure 2C).…”

“…Les régulations de la quantité de récepteurs de la PRL et de leur activité de modulation des signalisations intracellulaires, ainsi que de la PRL endogène, pourraient être des facteurs de progression des tumeurs mammaires et prostatiques [2,33,34]. Des effets combinés des formes PRL 23 kDa et 16K, cette dernière pouvant avoir une activité antitumorale, ont été envisagés dans la croissance de tumeurs de la prostate [35].…”