Triennial Lactation Symposium: Prolactin: The multifaceted potentiator of mammary growth and function.

At face value there are clear and established roles for prolactin (PRL) in the regulation of mammary gland growth, lactogenesis, and galactopoiesis. These actions of PRL do not occur in isolation; rather, they are finely attuned to and coordinated with many local, reproductive, and metabolic events in the female. Hence, to understand PRL action at the level of the mammary gland is to understand the systemic and local contexts in which it acts and functions. Herein we review the functions of PRL, its receptors, and the pathways leading to the phenotypes it evokes within the mammary glands, including growth and lactation, across a variety of species. At one level, the actions of PRL are mediated by several PRL receptor (PRLR) isoforms, including its long form and various short PRLR variants that are generated by alternative splicing in a species- and tissue-dependent manner. In turn, these PRLR activate a variety of intracellular signaling cascades. We also focus on how PRL coordinates with other endocrine cues to impart its effects on the mammary glands, where the ovarian hormones can independently and substantially modulate PRL action. Many of these effects of PRL are also realized at the local level of the mammary gland, either through the autocrine or paracrine synthesis of a multitude of molecules and transcription factors or through its effects on adjacent supporting tissues, including the mammary vasculature. Taken together, it is clear that PRL directs a variety of mechanisms during growth and function of the mammary gland and is deserving of its classification as the master hormone.