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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- "Oxytocin (OT) is a neuroendocrine hormone that is essential for normal breastfeeding physiology, as it stimulates breast myoepithelial cell contraction, which transfers milk to the areola for the infant (Pang and Hartmann, 2007). OT has been implicated in maternal behavior and in forming and maintaining social bonds, particularly in its interaction with dopamine (Pedersen et al., 1994; Pedersen, 1997; Numan et al., 2005; Aragona et al., 2006). "
ABSTRACT: Lactation is thought to buffer stress reactivity via oxytocin (OT). Dysregulation of the HPA axis has been reported in women with postpartum depression (PPD). The co-occurrence of PPD and lactation failure suggests that abnormalities in OT signaling may play a role in PPD. We hypothesized that abnormal OT signaling is implicated in dysregulated HPA axis reactivity among postpartum women with mood symptoms. In a prospective perinatal cohort, we tested associations between OT levels during breastfeeding and stress reactivity. We recruited 52 pregnant women who intended to breastfeed, among whom 47 underwent a standardized stressor, the Trier Social Stress Test (TSST), at 8 weeks postpartum. 39 were breastfeeding at time of TSST. We assessed mood symptoms using validated instruments and defined as symptomatic women with EPDS≥10 and/or Spielberger≥34. Following IV placement for blood draws, women breastfed their infants and then underwent the TSST. Mothers' hormone responses were quantified. Among symptomatic breastfeeding women (N=11; asymptomatic N=28), we found lower OT levels during breastfeeding (p<0.05) and higher CORT levels (p<0.05) both during breastfeeding and the TSST, as compared to asymptomatic breastfeeding women. In a mixed effects model examining CORT reactivity by symptom group and OT AUC, we observed a paradoxical response in symptomatic breastfeeding women during the TSST (group×time×OT AUC p<0.05); higher OT AUC was associated with higher CORT. In all breastfeeding women, the surge of OT during feeding appears to buffer subsequent stress-induced CORT secretion. However, in symptomatic breastfeeding women, we found a positive correlation between OT AUC and CORT, instead of the expected negative correlation, which we found among asymptomatic women. Copyright © 2015 Elsevier Ltd. All rights reserved.Psychoneuroendocrinology 02/2015; 55:164-172. DOI:10.1016/j.psyneuen.2015.02.009 · 5.59 Impact Factor
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- "OT has received less interest than gonadal or stress hormones as a potential etiologic factor in PPD, although it has attracted attention for its involvement in breastfeeding difficulties often present in PPD (Stuebe et al., 2012). It is well known that OT is critically implicated in milk letdown (Pang and Hartmann, 2007). The documented association between breastfeeding difficulties and PPD (Dennis and McQueen, 2009; Taveras et al., 2003; Watkins et al., 2011) is worthy of attention (Skalkidou et al., 2010). "
ABSTRACT: The role of oxytocin in the treatment of postpartum depression has been a topic of growing interest. This subject carries important implications, given that postpartum depression can have detrimental effects on both the mother and her infant, with lifelong consequences for infant socioemotional and cognitive development. In recent years, oxytocin has received attention for its potential role in many neuropsychiatric conditions beyond its well-described functions in childbirth and lactation. In the present review, we present available data on the clinical characteristics and neuroendocrine foundations of postpartum depression. We outline current treatment modalities and their limitations, and proceed to evaluate the potential role of oxytocin in the treatment of postpartum depression. The aim of the present review is twofold: a) to bring together evidence from animal and human research concerning the role of oxytocin in postpartum depression, and b) to highlight areas that deserve further research in order to bring a fuller understanding of oxytocin's therapeutic potential.Brain research 11/2013; 1580. DOI:10.1016/j.brainres.2013.11.009 · 2.83 Impact Factor
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- "The ratio of adipocytes to epithelia decreases to facilitate parenchymal expansion during this phase. A complex milieu of hormones marked by a drop in progesterone activates epithelial changes leading to lactation, which is typically maintained by the suckling response of the newborn (Neville et al. 2002; Pang and Hartmann 2007). Postlactation mammary involution, studied after natural or forced weaning, involves rapid regression of the differentiated gland and depends on programmed cell death pathways that eliminate up to 50% – 80% of the secretory epithelium within 1 wk of weaning (Walker et al. 1989). "
ABSTRACT: The adult mammary structure provides for the rapid growth, development, and immunological protection of the live-born young of mammals through its production of milk. The dynamic remodeling of the branched epithelial structure of the mammary gland in response to physiological stimuli that allow its programmed branching morphogenesis at puberty, cyclical turnover during the reproductive cycle, differentiation into a secretory organ at parturition, postlactational involution, and ultimately, regression with age is critical for these processes. Extracellular metalloproteinases are essential for the remodeling programs that operate in the tissue microenvironment at the interface of the epithelium and the stroma, coupling form with function. Deregulated proteolytic activity drives the transition of a physiological mammary microenvironment into a tumor microenvironment, facilitating malignant transformation.Cold Spring Harbor perspectives in biology 11/2010; 3(4). DOI:10.1101/cshperspect.a004333 · 8.23 Impact Factor