Initiation of human lactation: secretory differentiation and secretory activation.
ABSTRACT Theories for the origin of milk have been recorded since the time of Ancient Greeks. In those times it was believed that milk was derived from special vessels that connected the uterus to the breasts. The "chyle theory" on the origin of milk was another prominent theory which persisted well into the nineteenth century before the realisation that milk components were derived from blood and some milk constituents were actually synthesized within the breasts. The demonstration that milk ejection was the expulsion of milk that had already been secreted and that milk secretion was a separate continuous process, set the background for the development for the current understanding of milk synthesis and secretion. Today we know that there are two stages in the initiation of lactation- secretory differentiation and secretory activation. Secretory differentiation represents the stage of pregnancy when the mammary epithelial cells differentiate into lactocytes with the capacity to synthesize unique milk constituents such as lactose. This process requires the presence of a 'lactogenic hormone complex' of the reproductive hormones, estrogen, progesterone, prolactin and some metabolic hormones. Secretory activation on the other hand, is the initiation of copious milk secretion and is associated with major changes in the concentrations of many milk constituents. The withdrawal of progesterone triggers the onset of secretory activation but prolactin, insulin and cortisol must also be present. This review describes the works of pioneers that have led to our current understanding of the biochemical and endocrinological processes involved in the initiation of human lactation.
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ABSTRACT: Serotonin (5-hydroxytryptamine, 5-HT) is a very simple molecule that plays key roles in complex communication mechanisms within the animal body. In the mammary glands, serotonin biosynthesis and secretion are induced in response to dilation of the alveolar spaces. Since its discovery several years ago, mammary 5-HT has been demonstrated to perform two homeostatic functions. First, serotonin regulates lactation and initiates the transition into the earliest phases of involution. Second, serotonin is a local signal that induces parathyroid hormone-related peptide (PTHrP), which allows the mammary gland to drive the mobilization of calcium from the skeleton. These processes use different receptor types, 5-HT7 and 5-HT2, respectively. In this review, we provide synthetic perspectives on the fundamental processes of lactation homeostasis and the adaptation of calcium homeostasis for lactation. We analyze the role of the intrinsic serotonin system in the physiological regulation of the mammary glands. We also consider the importance of the mammary serotonin system in pathologies and therapies associated with lactation and breast cancer.02/2014; 2:353-74. DOI:10.1146/annurev-animal-022513-114227
Chapter: Lactation and its Hormonal Control[Show abstract] [Hide abstract]
ABSTRACT: The mammary gland undergoes its final development in the adult animal, filling the mammary fat pad with a ductal tree and rudimentary alveoli during puberty, and expanding and fully differentiating during pregnancy. The hormones of pregnancy, prolactin (PRL), placental lactogen, growth hormone, and progesterone (P4) cooperate to produce a gland that is fully developed but nonfunctional. Secretory activity commences around parturition, with the withdrawal of progesterone and maintained levels of PRL and glucocorticoid. During lactation PRL provides a comprehensive signal that fosters synthesis and secretion of milk components and the survival of the alveolar cell. The lactating gland produces milk of a composition defined for the species using several specialized pathways including: (1) exocytosis for the secretion of milk proteins, lactose and divalent ions; (2) a unique lipid secretion pathway that produces membrane-bound milk fat globules; (3) transport systems for monovalent ions, glucose, and amino acids; and (d) transcytosis for the secretion of immunoglobulins and other milk components. Tight junctions form a gasket around the apical surface of the epithelial cells that is open to traffic of large and small molecules in pregnancy but tightly closed in lactation. The volume of milk produced is determined by milk removal from the gland, a function dependent on oxytocin secretion by the posterior pituitary and contraction of myoepithelial cells to force milk out of the alveoli. With the termination of milk removal an orderly involution process involving interactions with immune cells returns the gland to its resting state. In short, we provide a summary of our present understanding of the cellular and molecular biology of mammary development and milk secretion in the context of the whole body mechanisms that ensure adequate flux of nutrients to the gland to provide sufficient milk to meet the needs of the neonate. This article is available through ScienceDirect through your library or online at: http://www.sciencedirect.com/science/article/pii/B97801239717530004Knobil and Neill's Physiology of Reproduction (Fourth Edition), 4th edited by Tony Plant, Anthony Zeleznik, 02/2015: chapter 46: pages 2055-2105; Elsevier., ISBN: ISBN-9780123971753