Multiple, PKA-dependent and PKA-independent, signals are involved in cAMP-induced PRL expression in the eosinophilic cell line Eol-1.
ABSTRACT Besides its pivotal role in reproduction, the polypeptide hormone prolactin (PRL) has been attributed an immunomodulatory function. Extrapituitary PRL expression is regulated differently from that in the pituitary, due to the use of an alternative promoter. In leukocytes, cAMP is an important regulator of PRL expression. We report that in the human eosinophilic cell line Eol-1, cAMP-induced PRL expression is partially abrogated by two protein kinase A (PKA) inhibitors (H89, PKI) and by the p38 inhibitor SB203580. Phosphorylation of p38 was PKA-independent and could be stimulated by a methylated cAMP analogue, which specifically activates the exchange factor directly activated by cAMP (EPAC). Furthermore, cAMP induced a PKA-dependent phosphorylation of cAMP-responsive element binding protein (CREB). We postulate that cAMP induces PRL expression via two different signalling pathways: a PKA-dependent pathway leading to the phosphorylation of CREB, and a PKA-independent pathway leading to the phosphorylation of p38.
Chapter: Prolactin in the Immune System[show abstract] [hide abstract]
ABSTRACT: Prolactin (PRL) is a protein hormone, as well as a cytokine, which is synthesized and secreted from specialized cells of the anterior pituitary gland, named lactotrophs. More than 300 functions exerted by PRL in vertebrates have been recognized; and they reflect the ubiquitous distribution of its receptors, as well as the fact that PRL is synthesized in many extrapituitary tissues. Among these sites of PRL synthesis are cells of the immune system, such as macrophages, natural killer cells, and T- and B-lymphocytes. Regulation of PRL synthesis is organ specific, which confers additional complexity to the spectrum of PRL actions. In the physiology of the immune system, PRL acts by stimulating the secretion of other cytokines and the expression of cytokine receptors, and also as a growth and survival factor. In pathological conditions, increased levels of PRL could cause deterioration of the subject’s condition. In this review, we integrate the information on regulation of PRL synthesis with that concerning its physiological and pathological actions in extrapituitary tissues, highlighting those in the immune system.01/2013: pages 53-82; , ISBN: 978-953-51-0943-3
Article: Antagonism of Taxol Cytotoxicity by Prolactin: Implication for Patient Resistance to Chemotherapy[show abstract] [hide abstract]
ABSTRACT: The overall objective of these studies is to examine the protective effects of prolactin (PRL) against anti-cancer drugs using MDA-MB-468 breast cancer cells and cisplatin as the experimental models. The major goal was to characterize the mechanism by which PRL provides chemoprotection. Progress has been made toward this goal as follows. First using flow cytometry we have established that cisplatin causes cell cycle arrest at the G2 phase. This was partially reversed by PRL. Second we found that cisplatin induces cell death by increasing early and late apoptotic events. This was prevented by pretreatment with PRL which likely acts by affecting cisplatin-induced DNA double strand breaks. Future studies will continue to explore the mechanism of chemoprotection by PRL.02/2008;