Prolactin receptor signal transduction in cells of the immune system

Abstract

Prolactin (PRL) was originally identified as a neuroendocrine hormone of pituitary origin (Riddle & Braucher 1931, Riddle et al. 1933). While the primary function of this hormone was initially thought to lie solely within the breast, the functional pleiotropism of this peptide with regards to reproduction, osmoregulation, and behavior was subsequently recognized (Nicoll 1974). Several lines of evidence have now also demonstrated an immunoregulatory role for this peptide. Structural analysis of PRL has revealed it to be related to members of the cytokine/ hematopoietin family such as growth hormone (GH), erythropoietin, granulocyte–macrophage colony stimulating factor (GM-CSF) and the interleukins (IL) IL-2 to IL-7 (Bazan 1990). Synthesis of PRL is not limited to the hypophysis, as numerous extra-pituitary sites of PRL expression including the decidua, breast, and T lymphocytes have been detected (DiMattia et al. 1986, Montogomery et al. 1987, Clevenger et al. 1990, Gellersen et al. 1994, Ginsburg & Vonderhaar 1995, Mershon et al. 1995, Clevenger & Plank 1997). The receptor for PRL (PRLr) is present on T and B lymphocytes and macrophages (Pellegrini et al. 1992, Dardenne et al. 1994). Acting through its receptor, PRL modulates immune system function by stimulating both cell proliferation and survival. Taken together, these data indicate that PRL acts at the endocrine, paracrine, and autocrine levels in regulating immune function (Gala 1991, Prystowsky & Clevenger 1994, Kooijman et al. 1996, Yu-Lee 1997). This review initially focuses on the immunoregulatory functions of PRL in the immune system, and then focuses on the structure/ function relationships within the PRLr as they pertain to immunologically relevant signal transduction pathways.