Prolactin and Mammary Gland Development

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Prolactin (PRL) regulates the development of themammary gland at three stages in the reproductive lifehistory of females. The first stage is mammary glandorganogenesis, during which PRL contributes to the maturation of the mammary glands from aprimary ductal system, which grows from terminal endbuds, to the fully mature nonpregnant gland. The maturemammary gland is characterized by an absence of terminal end buds, and the development of a highlybranched architecture, which is decorated by lobularbuds. During pregnancy PRL, placental lactogens, andprogesterone stimulate the expansion and physiological differentiation of the lobuloalveolar systemfrom the lobular buds. After delivery PRL, in thecontext of falling progesterone, stimulates the finalinduction of milk protein gene expression and lactation. PRL acts directly on the mammary epithelium,and indirectly by stimulating luteal progesteronesecretion in rodents. Disruption of the genes for PRLand the PRL receptor, as well as those for transcription factors important in mammary gland regulation(Stat proteins), have provided a new set of animalmodels with which to study normal mammary glanddevelopment and the relationships of PRL to breastcarcinogenesis. Two major deficiencies in our current knowledgeof PRL actions are our understanding of the role ofepithelial-stromal interactions in PRL-induced mammarymorphogenesis, and the identity of developmentally important genes that are regulated by PRLduring normal mammary gland organogenesis.