The neuroendocrine pituitary hormone Prolactin (PRL), also known as lactotrophin, mamotrophin, luteotropic hormone (LTH), or luteotropin, is a secreted hormone that affects reproduction and homeostasis in vertebrates. The functions of PRL can be placed in six broad categories: 1) reproduction and lactation; 2) growth and development; 3) endocrinology and metabolism; 4) brain and behavior; 5) immunomodulation; and 6) electrolyte balance (1, 2). PRL is secreted by the anterior pituitary gland, mammary gland, placenta, brain, uterus, decidua, dermal fibroblasts, B cells, T cells, NK cells, and some breast cancer cell lines. Although the major form of PRL is a 23 kDa monomeric protein, splice variants of 14, 16, and 22 kDa have been identified. PRL has also been found to be glycosylated, phosphorylated, dimerized, and polymerized. Glycosylation, phosphorylation, dimerization, or polymerization of PRL result in lower activity (2).
A single chain membrane-bound protein belonging to the class 1 cytokine superfamily mediates cell activation by PRL. The PRL receptor (PRL R) contains extracellular, transmembrane, and intracellular domains. Transcriptional regulation of the PRL R gene results in several different species-dependent isoforms of PRL R being produced. Although the cytoplasmic domains of the different isoforms vary in length and composition, their extracellular domains are identical. In mice, one long and three short forms of PRL receptor have been described (2). PRL receptors are found in mammary tissue, pituitary gland, brain, heart, lung thymus, spleen, liver, pancreas, kidney, adrenal gland, uterus, skeletal muscle and skin (3). A soluble form of PRL R containing the 206 NH2-terminal amino acids of the extracellular domain is secreted by mammary epithelial cells and is found in milk. Studies of PRL receptor deficient mice have demonstrated that PRL receptor signaling is required for female fertility and mammary development. Both male and female PRL receptor deficient mice have reduced bone formation and reduced abdominal fat deposits (1).