Regulation of Msx-1, Msx-2, Bmp-2 and Bmp-4 during foetal and postnatal mammary gland development

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2729-2737 ◽  
Author(s):  
D.J. Phippard ◽  
S.J. Weber-Hall ◽  
P.T. Sharpe ◽  
M.S. Naylor ◽  
H. Jayatalake ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Hormonal Regulation ◽  
Time Course ◽  
Mammary Gland Development ◽  
Cancer Cell Line ◽  
Mammary Development ◽  
Gene Products ◽  
Developmentally Regulated ◽  
Gland Development ◽  
Mcf 7

Expression of the Msx-1 and Msx-2 homeobox genes have been shown to be coordinately regulated with the Bmp-2 and Bmp-4 ligands in a variety of developing tissues. Here we report that transcripts from all four genes are developmentally regulated during both foetal and postnatal mammary gland development. The location and time-course of the Bmp and Msx expression point to a role for Msx and Bmp gene products in the control of epithelial-mesenchymal interactions. Expression of Msx-2, but not Msx-1, Bmp-2 or Bmp-4 was decreased following ovariectomy, while expression of the human Msx-2 homologue was regulated by 17beta-oestradiol in the MCF-7 breast cancer cell line. The regulation of Msx-2 expression by oestrogen raises the possibility that hormonal regulation of mammary development is mediated through the control of epithelial-mesenchymal interactions.

scholarly journals A Functional Connection between pRB and Transforming Growth Factor β in Growth Inhibition and Mammary Gland Development

2009 ◽  
Vol 29 (16) ◽  
pp. 4455-4466 ◽  
Author(s):  
Sarah M. Francis ◽  
Jacqueline Bergsied ◽  
Christian E. Isaac ◽  
Courtney H. Coschi ◽  
Alison L. Martens ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Growth Inhibition ◽  
Mammary Gland Development ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Mammary Development ◽  
Functional Connection ◽  
Gland Development

ABSTRACT Transforming growth factor β (TGF-β) is a crucial mediator of breast development, and loss of TGF-β-induced growth arrest is a hallmark of breast cancer. TGF-β has been shown to inhibit cyclin-dependent kinase (CDK) activity, which leads to the accumulation of hypophosphorylated pRB. However, unlike other components of TGF-β cytostatic signaling, pRB is thought to be dispensable for mammary development. Using gene-targeted mice carrying subtle missense changes in pRB (Rb1 ΔL and Rb1NF ), we have discovered that pRB plays a critical role in mammary gland development. In particular, Rb1 mutant female mice have hyperplastic mammary epithelium and defects in nursing due to insensitivity to TGF-β growth inhibition. In contrast with previous studies that highlighted the inhibition of cyclin/CDK activity by TGF-β signaling, our experiments revealed that active transcriptional repression of E2F target genes by pRB downstream of CDKs is also a key component of TGF-β cytostatic signaling. Taken together, our work demonstrates a unique functional connection between pRB and TGF-β in growth control and mammary gland development.

scholarly journals Strain-Specific Differences in the Mechanisms of Progesterone Regulation of Murine Mammary Gland Development

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1485-1494 ◽  
Author(s):  
Mark D. Aupperlee ◽  
Alexis A. Drolet ◽  
Srinivasan Durairaj ◽  
Weizhong Wang ◽  
Richard C. Schwartz ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Nuclear Factor Κb ◽  
Mammary Development ◽  
Normal Mammary Gland ◽  
Human Populations ◽  
Induced Expression ◽  
Altered Expression ◽  
Downstream Effectors ◽  
Gland Development

Progesterone (P) is required for normal mammary gland development, and is implicated in the etiology of mammary cancer in rodents and humans. We analyzed mammary gland developmental responses to P and estrogen (E) in two strains of mice (BALB/c and C57BL/6) that exhibit differences in ductal development at sexual maturity and alveologenesis during pregnancy. C57BL/6 mice exhibited reduced proliferative and morphological responses to P. Analysis of known mediators of sidebranching and alveologenesis revealed that reduced P-induced expression of P receptor isoform B and receptor activator of nuclear factor-κB ligand (RANKL), as well as altered expression and regulation of cyclin D1, CCAAT/enhancer binding protein β, and the downstream effectors of RANKL, nuclear Id2 and p21, contribute significantly to the reduced P responsiveness of the C57BL/6 mammary gland. In contrast, E responsiveness was greater in C57BL/6 than in BALB/c glands. E may play a compensatory role in C57BL/6 alveologenesis through its effect on the induction and activation of signal transducer and activator of transcription 5a, a known regulator of RANKL. These observations suggest that in human populations with heterogeneous genetic backgrounds, individuals may respond differentially to the same hormone. Thus, genetic diversity may have a role in determining the effects of P in normal mammary development and tumorigenesis. Reduced progesterone-induced expression of progesterone receptor and RANKL, altered expression and regulation of C/EBPβ, and of the downstream effectors of RANKL, nuclear Id2 and p21, contribute significantly to the reduced progesterone-responsiveness of the C57BL/6 mammary gland compared to the BALB/c gland.

scholarly journals Food intake dependent and independent effects of heat stress on lactation and mammary gland development

2020 ◽  
Author(s):  
Yao Xiao ◽  
Jason M. Kronenfeld ◽  
Benjamin J. Renquist
Keyword(s):  
Heat Stress ◽  
Mammary Gland ◽  
Food Intake ◽  
Milk Production ◽  
Mammary Gland Development ◽  
Heat Exposure ◽  
Mammary Development ◽  
Late Gestation ◽  
Independent Effects ◽  
Gland Development

ABSTRACTWith a growing population, a reliable food supply is increasingly important. Heat stress reduces livestock meat and milk production. Genetic selection of high producing animals increases endogenous heat production, while climate change increases exogenous heat exposure. Both sources of heat exacerbate the risk of heat-induced depression of production. Rodents are valuable models to understand mechanisms conserved across species. Heat exposure suppresses feed intake across homeothermic species including rodents and production animal species. We assessed the response to early-mid lactation or late gestation heat exposure on milk production and mammary gland development/function, respectively. Using pair-fed controls we experimentally isolated the food intake dependent and independent effects of heat stress on mammary function and mass. Heat exposure (35°C, relative humidity 50%) decreased daily food intake. When heat exposure occurred during lactation, hypophagia accounted for approximately 50% of the heat stress induced hypogalactia. Heat exposure during middle to late gestation suppressed food intake, which was fully responsible for the lowered mammary gland weight of dams at parturition. However, the impaired mammary gland function in heat exposed dams measured by metabolic rate and lactogenesis could not be explained by depressed food consumption. In conclusion, mice recapitulate the depressed milk production and mammary gland development observed in dairy species while providing insight regarding the role of food intake. This opens the potential to apply genetic, experimental and pharmacological models unique to mice to identify the mechanism by which heat is limiting animal production.Summary StatementsThis study demonstrates that heat stress decreases lactation and mammary development through food intake dependent and independent mechanisms.

scholarly journals Baicalin Promotes Mammary Gland Development via Steroid-Like Activities

2021 ◽  
Vol 9 ◽  
Author(s):  
Weizhen Chen ◽  
Wei Wei ◽  
Liya Yu ◽  
Xin Zhang ◽  
Fujing Huang ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Tumor Growth ◽  
Cell Line ◽  
Cancer Progression ◽  
Mammary Gland Development ◽  
Biological Activities ◽  
Xenograft Model ◽  
Mammary Development ◽  
Tumor Xenograft ◽  
Gland Development

Baicalin, the main flavonoid component extracted from Scutellaria roots, has a variety of biological activities and is therefore used in the treatment of many kinds of diseases. However, whether baicalin affects the normal development of tissues and organs is still unclear. Here, using a mouse mammary gland model, we investigated the effects of baicalin on the expansion of mammary stem cells (MaSCs) and mammary development, as well as breast cancer progression. Interestingly, we found that baicalin administration significantly accelerates duct elongation at puberty, and promotes alveolar development and facilitates milk secretion during pregnancy. Furthermore, self-renewal of MaSCs was significantly promoted in the presence of baicalin. Moreover, in a tumor xenograft model, baicalin promoted tumor growth of the MDA-MB-231 cell line, but suppressed tumor growth of the ZR-751 cell line. Mechanistically, baicalin can induce expression of the protein C receptor, while inhibiting the expression of the estrogen receptor. Transcriptome analysis revealed that baicalin is involved in signaling pathways related to mammary gland development, immune response, and cell cycle control. Taken together, our results from comprehensive investigation of the biological activity of baicalin provide a theoretical basis for its rational clinical application.

Normal mammary gland growth and lactation capacity in pregnant relaxin-deficient mice

2009 ◽  
Vol 21 (4) ◽  
pp. 549 ◽  
Author(s):  
Laura J. Parry ◽  
Lenka A. Vodstrcil ◽  
Anna Madden ◽  
Stephanie H. Amir ◽  
Katrina Baldwin ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mammary Gland ◽  
Milk Protein ◽  
Mammary Gland Development ◽  
Mammary Development ◽  
Normal Mammary Gland ◽  
Pregnant Mice ◽  
Ductal Branching ◽  
Pup Mortality ◽  
Gland Development

Pups born to mice with a targeted deletion of relaxin or its receptor (Rxfp1) die within 24 h postpartum. This has been attributed, in part, to abnormal mammary gland development in relaxin-mutant mice (Rln–/–). However, mammary development is normal in relaxin receptor-mutant (Rxfp1–/–) mice. The present study aimed to verify the mammary phenotypes in late pregnant and early lactating Rln–/– mice and to test the hypothesis that relaxin is involved in milk protein synthesis. Comparisons between late pregnant and early lactating wildtype (Rln+/+) and Rln–/– mice showed no differences in lobuloalveolar structure or ductal branching in the mammary gland. Mammary explants from Rln–/– mice also expressed β-casein and α-lactalbumin in response to lactogenic hormones at a similar level to Rln+/+ mice, implying normal milk protein synthesis. Pregnant Rln–/– mice infused with relaxin for 6 days gave birth to live pups without difficulty, and 96% of pups survived beyond 7 days. This is in contrast with the 100% pup mortality in saline-treated Rln–/– mice or 3-day relaxin-treated Rln–/– mice. Pups born to relaxin-treated Rln–/– dams weighed significantly less than Rln+/+ pups but had similar growth rates as their wildtype counterparts. In summary, relaxin is not critical for mammary gland development or β-casein and α-lactalbumin expression in late pregnant mice. In addition, Rln–/– dams did not need to be treated with relaxin postpartum for the pups to survive, suggesting that relaxin has no role in the maintenance of lactation in mice.

SELF-LICKING AND MAMMARY DEVELOPMENT DURING PREGNANCY IN THE RAT

1968 ◽  
Vol 42 (3) ◽  
pp. 363-NP ◽  
Author(s):  
L. L. ROTH ◽  
J. S. ROSENBLATT
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Post Partum ◽  
Mammary Development ◽  
Entire Period ◽  
External Stimulation ◽  
Stress Effects ◽  
Secretory Tissue ◽  
Gland Development ◽  
Stimulation Of

SUMMARY Stimulation of the nipple lines and genital and pelvic regions by self-licking, found previously to increase during pregnancy in the rat, was studied for its effect on mammary gland development. Licking was prevented by fitting wide rubber collars around the necks of rats for the entire period of pregnancy or for either the first half (days 1–12) or the second half (days 12–22) of pregnancy. The percentage of secretory tissue, and ratings of lobulo-alveolar (L-A) development and secretory (S) activity were used to measure the development of the gland on either the 22nd or the 12th day of pregnancy. Notched collars, which permitted licking, were used as a control for any stress effects that resulted from the collars, and injections of formalin were used as a control for any stress produced by the collar. Mammary development was reduced to only 50% of normal, and L-A development and S-activity ratings showed a corresponding retarded development in animals wearing a collar throughout pregnancy. Notched collars did not affect gland development and formalin injections accelerated it. There was no difference in the effects of wearing a collar during the first or second half of pregnancy: both groups were equal in gland development on the 22nd day and their glands were more developed than those of females wearing a collar throughout pregnancy. In animals that wore collars from the beginning of pregnancy, gland development was already retarded (28%) by mid-pregnancy. Rats whose glands were reduced in development during the first half of pregnancy showed less nipple-line licking during the second half of pregnancy. These findings indicate that stimulation provided by self-licking contributes significantly to mammary gland development during pregnancy and, therefore, the activity of the gland before parturition, like lactation post partum, is regulated in part by external stimulation.

scholarly journals Mammary development in the embryo and adult: new insights into the journey of morphogenesis and commitment

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev169862
Author(s):  
Christine J. Watson ◽  
Walid T. Khaled
Keyword(s):  
Mammary Gland ◽  
Progenitor Cell ◽  
Mammary Gland Development ◽  
Mammary Development ◽  
Three Dimensions ◽  
Lineage Specification ◽  
Technological Advances ◽  
Mammary Stem ◽  
Psychosocial Benefits ◽  
Gland Development

ABSTRACTThe mammary gland is a unique tissue and the defining feature of the class Mammalia. It is a late-evolving epidermal appendage that has the primary function of providing nutrition for the young, although recent studies have highlighted additional benefits of milk including the provision of passive immunity and a microbiome and, in humans, the psychosocial benefits of breastfeeding. In this Review, we outline the various stages of mammary gland development in the mouse, with a particular focus on lineage specification and the new insights that have been gained by the application of recent technological advances in imaging in both real-time and three-dimensions, and in single cell RNA sequencing. These studies have revealed the complexity of subpopulations of cells that contribute to the mammary stem and progenitor cell hierarchy and we suggest a new terminology to distinguish these cells.

scholarly journals Elevated Circulating IGF-I Promotes Mammary Gland Development and Proliferation

Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5751-5761 ◽  
Author(s):  
Dara Cannata ◽  
Danielle Lann ◽  
Yingjie Wu ◽  
Sebastien Elis ◽  
Hui Sun ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Animal Studies ◽  
Mammary Gland Development ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Epithelial Development ◽  
Igf I ◽  
Luminal Cells ◽  
Gland Development ◽  
Major Mediator

Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. In the present study we used the hepatic IGF-I transgenic (HIT) and IGF-I knockout/HIT (KO-HIT) mouse models to examine the effects of enhanced circulating IGF-I on mammary development in the presence and absence of local IGF-I. HIT mice express the rat IGF-I transgene under the transthyretin promoter in the liver and have elevated circulating IGF-I and normal tissue IGF-I levels. The KO-HIT mice have no tissue IGF-I and increased circulating IGF-I. Analysis of mammary gland development reveals a greater degree of complexity in HIT mice as compared to control and KO-HIT mice, which demonstrate similar degrees of mammary gland complexity. Immunohistochemical evaluation of glands of HIT mice also suggests an enhanced degree of proliferation of the mammary gland, whereas KO-HIT mice exhibit mammary gland proliferation similar to control mice. In addition, HIT mice have a higher percentage of proliferating myoepithelial and luminal cells than control mice, whereas KO-HIT mice have an equivalent percentage of proliferating myoepithelial and luminal cells as control mice. Thus, our findings show that elevated circulating IGF-I levels are sufficient to promote normal pubertal mammary epithelial development. However, HIT mice demonstrate more pronounced mammary gland development when compared to control and KO-HIT mice. This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation.

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