scholarly journals Autocrine regulation of milk secretion by a protein in milk

1995 ◽  
Vol 305 (1) ◽  
pp. 51-58 ◽  
Author(s):  
C J Wilde ◽  
C V P Addey ◽  
L M Boddy ◽  
M Peaker
Keyword(s):  
Mammary Gland ◽  
Whey Protein ◽  
Mammary Epithelial Cells ◽  
Feedback Inhibition ◽  
Primary Cultures ◽  
Milk Proteins ◽  
Mammary Epithelial ◽  
Milk Secretion ◽  
Lactating Goats ◽  
Lactating Mammary Gland

Frequency or completeness of milk removal from the lactating mammary gland regulates the rate of milk secretion by a mechanism which is local, chemical and inhibitory in nature. Screening of goat's milk proteins in rabbit mammary explant cultures identified a single whey protein of M(r) 7600 able to inhibit synthesis of milk constituents. The active whey protein, which we term FIL (Feedback inhibitor of Lactation), also decreased milk secretion temporarily when introduced into a mammary gland of lactating goats. FIL was synthesized by primary cultures of goat mammary epithelial cells, and was secreted vectorially together with other milk proteins. N-terminal amino acid sequencing indicated that it is a hitherto unknown protein. The evidence indicates that local regulation of milk secretion by milk removal is through autocrine feedback inhibition by this milk protein.

scholarly journals ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution

2018 ◽  
Vol 315 (2) ◽  
pp. R323-R335 ◽  
Author(s):  
Olivia C. Rivera ◽  
Stephen R. Hennigar ◽  
Shannon L. Kelleher
Keyword(s):  
Cell Death ◽  
Mammary Gland ◽  
Mammary Epithelial Cells ◽  
Tissue Remodeling ◽  
Vacuolar Atpase ◽  
Mammary Epithelial ◽  
Direct Role ◽  
Lysosome Biogenesis ◽  
Mammary Gland Involution ◽  
Lactating Mammary Gland

Mammary gland involution, a tightly regulated process of tissue remodeling by which a lactating mammary gland reverts to the prepregnant state, is characterized by the most profound example of regulated epithelial cell death in normal tissue. Defects in the execution of involution are associated with lactation failure and breast cancer. Initiation of mammary gland involution requires upregulation of lysosome biogenesis and acidification to activate lysosome-mediated cell death; however, specific mediators of this initial phase of involution are not well described. Zinc transporter 2 [ZnT2 ( SLC30A2)] has been implicated in lysosome biogenesis and lysosome-mediated cell death during involution; however, the direct role of ZnT2 in this process has not been elucidated. Here we showed that ZnT2-null mice had impaired alveolar regression and reduced activation of the involution marker phosphorylated Stat3, indicating insufficient initiation of mammary gland remodeling during involution. Moreover, we found that the loss of ZnT2 inhibited assembly of the proton transporter vacuolar ATPase on lysosomes, thereby decreasing lysosome abundance and size. Studies in cultured mammary epithelial cells revealed that while the involution signal TNFα promoted lysosome biogenesis and acidification, attenuation of ZnT2 impaired the lysosome response to this involution signal, which was not a consequence of cytoplasmic Zn accumulation. Our findings establish ZnT2 as a novel regulator of vacuolar ATPase assembly, driving lysosome biogenesis, acidification, and tissue remodeling during the initiation of mammary gland involution.

scholarly journals Oestradiol enhances apoptosis in bovine mammary epithelial cells in vitro

2012 ◽  
Vol 80 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Lucile Yart ◽  
Laurence Finot ◽  
Vanessa Lollivier ◽  
Frederic Dessauge
Keyword(s):  
Mammary Gland ◽  
Milk Production ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial Cells ◽  
Major Effect ◽  
Mammary Epithelial ◽  
Bovine Mammary Epithelial Cells ◽  
Lactating Mammary Gland ◽  
Negative Effect

Ovarian steroids, oestradiol and progesterone, are required for normal mammary growth at puberty and during pregnancy. They contribute to mammary parenchyma development by stimulating mammary epithelial cell (MEC) proliferation. However several studies demonstrate that oestradiol negatively affects milk production during the declining phase of lactation, but the oestradiol effect on MEC in lactating mammary gland remains unclear. The objective of this study was to investigate the differential effect of oestradiol on bovine MECs mimicking two physiological statuses: active and early apoptotic MECs. We demonstrated that oestradiol has a major effect on early apoptotic MECs and might accelerate MEC apoptosis by activation of caspases rather than by inducing apoptosis in active MECs. Early apoptotic MECs could be compared with senescent cells in the late-lactation mammary gland. These results suggest that the negative effect of oestradiol on milk production during the declining phase of lactation would be due to an enhancement of apoptotic processes in MECs.

Role of extracellular matrix and prolactin in functional differentiation of bovine BME-UV1 mammary epithelial cells

2011 ◽  
Vol 14 (3) ◽  
pp. 433-442 ◽  
Author(s):  
M. Kozłowski ◽  
J. Wilczak ◽  
T. Motyl ◽  
M. Gajewska
Keyword(s):  
Extracellular Matrix ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Culture System ◽  
Mammary Epithelial Cells ◽  
3D Culture ◽  
Milk Proteins ◽  
Functional Differentiation ◽  
Mammary Epithelial

Role of extracellular matrix and prolactin in functional differentiation of bovine BME-UV1 mammary epithelial cells Interactions between extracellular matrix (ECM) and epithelial cells are necessary for proper organisation and function of the epithelium. In the present study we show that bovine mammary epithelial cell line BME-UV1 cultured on ECM components, commercially available as Matrigel™, constitutes a good model for studying mechanisms controlling functional differentiation of the bovine mammary gland. In contact with Matrigel BME-UV1 cells induce apicobasal polarity, and within 16 days form three dimensional (3D) acinar structures with a centrally localized hollow lumen, which structurally resemble mammary alveoli present in the functionally active mammary gland. We have shown that the 3D culture system enables a high expression and proper localisation of integrin receptors and tight junction proteins in BME-UV1 cells to be induced. This effect was not obtained in cells grown in the classical 2D culture system on plastic. Moreover, ECM highly stimulated the synthesis of one of the major milk proteins, β-casein, even in the absence of prolactin. Our results show that contact with ECM plays an important role in the lactogenic activity of bovine MECs, however, prolactin is necessary for the efficient secretion of milk proteins.

scholarly journals The insulin receptor plays an important role in secretory differentiation in the mammary gland

2013 ◽  
Vol 305 (9) ◽  
pp. E1103-E1114 ◽  
Author(s):  
Margaret C. Neville ◽  
Patricia Webb ◽  
Palaniappan Ramanathan ◽  
Meridee P. Mannino ◽  
Chiara Pecorini ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Insulin Receptor ◽  
Lipid Droplets ◽  
Mammary Epithelial Cells ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Expression Of Genes ◽  
Lactating Mammary Gland ◽  
Development And Differentiation ◽  
Pregnant Mice

Insulin is known to be an important regulator of milk secretion in the lactating mammary gland. Here we examine the role of insulin signaling in mammary development in pregnancy using a mouse with a floxed insulin receptor (IR) crossed with a mouse expressing Cre specifically in the mammary gland. In the mammary glands of these IRfl/fl Cre+ mice, expression of IR is significantly diminished throughout development. Glands from these mice had 50% fewer alveoli at midpregnancy; casein and lipid droplets were diminished by 60 and 75%, respectively, indicating a role for IR both in alveolar development and differentiation. In an acinar preparation from mammary epithelial cells (MEC) isolated from pregnant mice, insulin stimulated lumen formation, mammary cell size, acinar size, acinar casein content, and the formation of lipid droplets with a Km of ∼1.7 nM. IGF-I and IGF-II had no effect at concentrations below 50 nM, and a function blocking antibody to the IGF type 1 receptor did not alter the response to insulin. We conclude that insulin interacting with IR is essential for mammary differentiation during murine pregnancy. Using array analysis, we then examined the expression of genes up- or downregulated >1.5-fold in the IRfl/fl Cre+ MECs, finding significant downregulation of differentiation specific genes and upregulation of cell cycle and extracellular matrix genes. We conclude that insulin fosters differentiation and may inhibit cell proliferation in the mammary gland of the midpregnant mouse.

scholarly journals ZnT4 provides zinc to zinc-dependent proteins in the trans-Golgi network critical for cell function and Zn export in mammary epithelial cells

2012 ◽  
Vol 303 (3) ◽  
pp. C291-C297 ◽  
Author(s):  
Nicholas H. McCormick ◽  
Shannon L. Kelleher
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Cell Membrane ◽  
Cell Function ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Milk Secretion ◽  
Trans Golgi Network ◽  
Dependent Protein ◽  
Golgi Network

Zinc (Zn) transporter 4 (ZnT4) plays a key role in mammary gland Zn metabolism. A mutation in ZnT4 ( SLC30A4) that targets the protein for degradation is responsible for the “lethal milk” ( lm/lm) mouse phenotype. ZnT4 protein is only detected in the secreting mammary gland, and lm/lm mice have ∼35% less Zn in milk, decreased mammary gland size, and decreased milk secretion. However, the precise contribution of ZnT4 is unknown. We used cultured mouse mammary epithelial cells (HC11) and determined that ZnT4 was localized to the trans-Golgi network (TGN) and cell membrane and transported Zn from the cytoplasm. ZnT4-mediated Zn import into the TGN directly contributed to labile Zn accumulation as ZnT4 overexpression increased FluoZin3 fluorescence. Moreover, ZnT4 provided Zn for metallation of galactosyltransferase, a Zn-dependent protein localized within the TGN that is critical for milk secretion, and carbonic anhydrase VI, a Zn-dependent protein secreted from the TGN into milk. We further noted that ZnT4 relocalized to the cell membrane in response to Zn. Together these studies demonstrated that ZnT4 transports Zn into the TGN, which is critical for key secretory functions of the mammary cell.

scholarly journals Evidence of Rab3A Expression, Regulation of Vesicle Trafficking, and Cellular Secretion in Response to Heregulin in Mammary Epithelial Cells

2000 ◽  
Vol 20 (23) ◽  
pp. 9092-9101 ◽  
Author(s):  
Ratna K. Vadlamudi ◽  
Rui-An Wang ◽  
Amjad H. Talukder ◽  
Liana Adam ◽  
Randy Johnson ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Vesicle Trafficking ◽  
Mammary Epithelial ◽  
Coated Vesicle ◽  
Human Breast ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Stimulation Of

ABSTRACT Heregulin β1 (HRG), a combinatorial ligand for human growth factor receptors 3 and 4, is a regulatory polypeptide that promotes the differentiation of mammary epithelial cells into secretory lobuloalveoli. Emerging evidence suggests that the processes of secretory pathways, such as biogenesis and trafficking of vesicles in neurons and adipose cells, are regulated by the Rab family of low-molecular-weight GTPases. In this study, we identified Rab3A as a gene product induced by HRG. Full-length Rab3A was cloned from a mammary gland cDNA library. We demonstrated that HRG stimulation of human breast cancer cells and normal breast epithelial cells induces the expression of Rab3A protein and mRNA in a cycloheximide-independent manner. HRG-mediated induction of Rab3A expression was blocked by an inhibitor of phosphatidylinositol 3-kinase but not by inhibitors of mitogen-activated protein kinases p38MAPK and p42/44MAPK. Human breast epithelial cells also express other components of regulated vesicular traffic, such as rabphilin 3A, Doc2, and syntaxin. Rab3A was predominantly localized in the cytosol, and HRG stimulation of the epithelial cells also raised the level of membrane-bound Rab3A. HRG treatment induced a profound alteration in the cell morphology in which cells displayed neuron-like membrane extensions that contained Rab3A-coated, vesicle-like structures. In addition, HRG also promoted the secretion of cellular proteins from the mammary epithelial cells. The ability of HRG to modify exocytosis was verified by using a growth hormone transient-transfection system. Analysis of mouse mammary gland development revealed the expression of Rab3A in mammary epithelial cells. Furthermore, expression of the HRG transgene in Harderian tumors in mice also enhanced the expression of Rab3A. These observations provide new evidence of the existence of a Rab3A pathway in mammary epithelial cells and suggest that it may play a role in vesicle trafficking and secretion of proteins from epithelial cells in response to stimulation by the HRG expressed within the mammary mesenchyma.

Sign in / Sign up

Export Citation Format

Share Document