Extrapituitary Prolactin: Distribution, Regulation, Functions, and Clinical Aspects*

Abstract

PRL affects more physiological processes than all other pituitary hormones combined. Among these are the regulation of mammary gland development, initiation and maintenance of lactation, immune modulation, osmoregulation, and behavioral modification. At the cellular level, PRL exerts mitogenic, morphogenic, or secretory activities. This raises the question as to the mechanism by which a single hormone can modulate so many seemingly unrelated functions. This review addresses the concept of the dual function of PRL, as a circulating hormone and a cytokine. The diversity of PRL actions is derived from three components: structural polymorphism, local production and processing, and divergent intracellular signaling pathways and target genes. PRL can be easily classified as a cytokine based on its shared properties with hematopoietic growth factors. These include comparable structural motifs, multiple sites of synthesis, ubiquitous receptor distribution, homologous receptor structure, and similar signal transduction pathways. A seminal report by Nagy and Berczi (1) drew attention to extrapituitary PRL. They reported that hypophysectomized female rats had 10–20% lactogenic activity in their serum as compared with controls. Within 2 months, the lactogenic activity gradually increased to 50% of controls.