scholarly journals Local Insulin-Like Growth Factor-II Mediates Prolactin-Induced Mammary Gland Development

2003 ◽  
Vol 17 (3) ◽  
pp. 460-471 ◽  
Author(s):  
Russell C. Hovey ◽  
Jessica Harris ◽  
Darryl L. Hadsell ◽  
Adrian V. Lee ◽  
Christopher J. Ormandy ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Early Pregnancy ◽  
Insulin Receptors ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
Receptor Expression ◽  
Mammary Tissue ◽  
Alveolar Development

Abstract Prolactin (PRL) is a major determinant of mammary epithelial cell proliferation during alveolar development in sexually mature and pregnant mice. To date, it has not been clear whether PRL effects these responses alone or by also invoking the action of autocrine/paracrine growth factors. In this study, we provide evidence that part of the effect of PRL on mammary gland growth is mediated by IGF-II. During sexual maturity and in early pregnancy, the level of IGF-II mRNA in the mammary gland was increased concurrent with increased PRL receptor expression. The level of IGF-II mRNA was reduced in mammary tissue from PRL receptor−/− mice during early pregnancy, and explants of mouse mammary gland and HC11 mammary epithelial cells both increased their expression of IGF-II after exposure to PRL in vitro. These findings coincided with the demonstration that IGF-II stimulated alveolar development in mammary glands in whole organ culture. PRL was most efficacious in stimulating IGF-II gene transcription from promoter 3 of the mouse IGF-II gene in vitro. Insight into the mechanism by which PRL induced IGF-II expression was provided by the fact that it was blocked by the Jak2 inhibitor AG490 and the MAPK inhibitor PD98059. Finally, induction of insulin receptor substrate (IRS)-1 in the mammary glands of PRL-treated mice and induction of IRS-1 and IRS-2 after treatment with PRL plus progesterone indicates that these molecules are induced by PRL as potential signaling intermediates downstream from IGF-I/insulin receptors. Together, these data demonstrate a role for IGF-II as a mediator of PRL action in the mouse mammary gland during ductal branching and alveolar development.

INTERACTION BETWEEN PROLACTIN AND THYROXINE IN MOUSE MAMMARY GLAND LOBULO-ALVEOLAR DEVELOPMENT IN VITRO

1969 ◽  
Vol 45 (4) ◽  
pp. 579-583 ◽  
Author(s):  
D. V. SINGH ◽  
H. A. BERN
Keyword(s):  
Mammary Gland ◽  
Synergistic Effects ◽  
Synthetic Medium ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Intact Female ◽  
Antagonistic Effects ◽  
Alveolar Development ◽  
Development In Vitro

SUMMARY Intact female BALB/cCrgl mice, 3–4 weeks old, were pretreated with oestrogen and progesterone for 9 days. Whole mammary glands from these mice were cultivated for 5 days in a synthetic medium supplemented with aldosterone (A), prolactin (MH) and insulin (I), with and without thyroxine (T4) at concentrations ranging from 0·01 to 5 μg./ml. A medium containing 1 μg. A +5 μg.MH +5 μg.I/ml. was generally optimal for lobulo-alveolar development. Addition of thyroxine to this combination resulted in a decrease in development which was highly significant at higher concentrations. However, when cultures were maintained in media containing suboptimal or low amounts of prolactin (1 μg. A + 3 μg. MH +5 μg. I/ml. and 1 μg. A + 1 μg. MH +5 μg. I/ml., respectively), the results indicate two possible effects of thyroxine: lower amounts of thyroxine had synergistic effects, whereas greater amounts had antagonistic effects on lobulo-alveolar development.

Differential expression of the growth hormone receptor and growth hormone-binding protein in epithelia and stroma of the mouse mammary gland at various physiological stages

1999 ◽  
Vol 161 (1) ◽  
pp. 77-87 ◽  
Author(s):  
YN Ilkbahar ◽  
G Thordarson ◽  
IG Camarillo ◽  
F Talamantes
Keyword(s):  
Growth Hormone ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Growth Hormone Receptor ◽  
Mammary Epithelial Cells ◽  
Late Pregnancy ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
Mrna Levels

Increasing evidence suggests that GH is important in normal mammary gland development. To investigate this further, we studied the distribution and levels of growth hormone receptor (GHR) and GH-binding protein (GHBP) in the mouse mammary gland. At three weeks of age, the epithelial component of the right fourth inguinal mammary gland of female mice was removed. These animals were then either maintained as virgins until they were killed or they were mated. One group of the mated mice was killed on day 18 of pregnancy and the remaining mated animals were allowed to carry their pups until term and were killed on day 6 of lactation. At the time of death, both the intact left and the de-epithelialized right mammary glands were collected from all three groups. Some of the intact glands served as a source of epithelial cells, free of stroma. The mRNA levels for GHR and GHBP were measured in intact glands, epithelia-cleared fat pads, and isolated mammary epithelial cells. GHR and GHBP mRNAs were expressed in both the mammary epithelium and stroma. However, the levels of both GHR and GHBP mRNAs were significantly higher in the stroma as compared with the epithelium component. This increase for both mRNAs was from 3- to 12-fold at each physiological state examined. In the intact gland, both GHR and GHBP transcripts were highest in virgins, declined during late pregnancy, and the lowest levels were found in the lactating gland. GHBP and GHR protein concentrations were also assessed in intact glands and epithelia-free fat pads. Similar to the mRNAs, GHR and GHBP protein levels (means+/-s.e.m.) in intact glands were highest in virgin mice (0.891+/-0.15 pmoles/mg protein and 0.136+/-0.26 pmoles/mg protein respectively), declined during late pregnancy (0. 354+/-0.111 pmoles/mg protein and 0.178+/-0.039 pmoles/mg protein respectively), and were lowest during lactation (0.096+0.037 pmoles/mg protein and 0.017+0.006 pmoles/mg protein respectively). Immunocytochemistry utilizing specific antisera against mouse (m) GHR and mGHBP revealed that the two proteins are localized to both the stroma and parenchyma of mouse mammary glands, with similar patterns of immunostaining throughout the different physiological stages analyzed. GHR immunolocalized to the plasma membrane and cytosol of mammary epithelial cells and adipocytes, whereas the GHBP immunostaining was nuclear and cytosolic. In conclusion, we report here that GHR and GHBP mRNAs and proteins are expressed in both the epithelium and the stroma of mammary glands of virgin, pregnant, and lactating mice. In intact glands, GHR and GHBP proteins, as well as their transcripts are higher in abundance in virgin relative to lactating mice. At all physiological stages, GHR and GHBP mRNA levels are higher in the stroma compared with the parenchyma. These findings indicate that the actions of GH in the mammary gland are both direct through its binding to the epithelia, and indirect by binding to the stroma and stimulation of IGF-I production which, in turn, affects mammary epithelial development.

scholarly journals Altered mammary epithelial development, pattern formation and involution in transgenic mice expressing the EphB4 receptor tyrosine kinase

2002 ◽  
Vol 115 (1) ◽  
pp. 25-37
Author(s):  
Nadia Munarini ◽  
Richard Jäger ◽  
Susanne Abderhalden ◽  
Gisela Zuercher ◽  
Valeria Rohrbach ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Transgenic Mice ◽  
Apoptotic Cell ◽  
Mammary Epithelium ◽  
Transgenic Animals ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
Cellular Growth ◽  
Mmtv Ltr

We have previously documented the cell-type-specific and hormone-dependent expression of the EphB4 receptor in the mouse mammary gland. To investigate its role in the biology of the mammary gland, we have established transgenic mice bearing the EphB4 receptor under the control of the MMTV-LTR promoter, which represents the first transgenic mouse model to investigate the effect(s) of unscheduled expression of EphB4 in adult organisms. Transgene expression in the mammary epithelium was induced at puberty, increased during pregnancy, culminated at early lactation and persisted until day three of post-lactational involution. In contrast, expression of the endogenous EphB4 gene is downregulated during pregnancy, is essentially absent during lactation and is re-induced after day three of post-lactational involution. The unscheduled expression of EphB4 led to a delayed development of the mammary epithelium at puberty and during pregnancy. During pregnancy, less lobules were formed, these however exhibited more numerous but smaller alveolar units. Transgenic mammary glands were characterized by a fragile, irregular morphology at lactation; however, sufficient functionality was maintained to nourish the young. Transgenic mammary glands exhibited untimely epithelial apoptotic cell death during pregnancy and abnormal epithelial DNA synthesis at early post-lactational involution, indicating a disturbed response to proliferative/apoptotic signals. Mammary tumours were not observed in the EphB4 transgenic animals; however, in double transgenic animals expressing both EphB4 and the neuT genes, tumour appearance was significantly accelerated and, in contrast to neuT-only animals, metastases were observed in the lung. These results implicate EphB4 in the regulation of tissue architecture, cellular growth response and establishment of the invasive phenotype in the adult mammary gland.

scholarly journals Exposure to the Endocrine Disruptor, Propylparaben, During Pregnancy and Lactation, Alters Typical Parity-Induced Reorganization of the Mouse Mammary Gland

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A487-A488
Author(s):  
Joshua Philip Mogus
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Cancer Risk ◽  
Immune Cell ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Receptor Expression ◽  
Intermediate Phenotypes ◽  
Sensitive Organ ◽  
Pregnancy And Lactation

Abstract The mammary gland is a hormone sensitive organ that is susceptible to endocrine disrupting chemicals (EDCs) during several vulnerable periods, including pregnancy and lactation. Mammary gland reorganization during pregnancy and lactation is hormone driven and provides long-term protection against breast cancer risk. It is unknown if EDC exposures during these sensitive windows can alter mammary reorganization to either enhance or offset parity-induced protection against breast cancer. Here, we examined effects of propylparaben (PP), a common preservative used in personal care products and foods with estrogen receptor (ER) agonist properties, on the parous mouse mammary gland. Pregnant BALB/c mice were treated with 0, 20, 100, or 10,000 µg/kg/day PP throughout pregnancy and lactation. These doses were selected for their relevance to human exposures. We also included an unexposed nulliparous female group to evaluate the typical changes associated with parity. Five weeks post-involution (and five weeks after the last PP exposure), mammary glands were collected and assessed for changes in histomorphology, hormone receptor expression, immune cell number, and gene expression. We found that PP reduced many of the typical morphological effects of parity on the mammary gland, resulting in intermediate phenotypes for ductal density and total epithelial structures. Notably, we found increased proliferation in PP-treated mammary glands, despite decreased ductal epithelial volume relative to parous controls. Mammary glands from PP-treated females also had alterations in the expression of ERα-mediated genes, including PgR (the gene that encodes progesterone receptor) and Igf1, with expression levels that were intermediate to both nulliparous and parous control mice. Finally, PP reduced the effect of parity on several immune cell types in the mammary gland including B cells, T-cells, and M2 macrophages. These results suggest that PP, at levels relevant to human exposure, can disrupt the normal response to parity in the mouse mammary gland, including persistent alterations to mammary gland structures. Future studies should address whether PP exposures disturb the protective effects of pregnancy on mammary cancer risk.

scholarly journals Arginine Supply Impacts the Expression of Candidate microRNA Controlling Milk Casein Yield in Bovine Mammary Tissue

Animals ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 797 ◽  
Author(s):  
Xin Zhang ◽  
Yifan Wang ◽  
Mengzhi Wang ◽  
Gang Zhou ◽  
Lianmin Chen ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Milk Protein ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
In Vivo Study ◽  
Mammary Tissue ◽  
Casein Synthesis

Arginine, a semi-essential functional amino acid, has been found to promote the synthesis of casein in mammary epithelial cells to some extent. Data from mouse indicated that microRNA (miRNA) are important in regulating the development of mammary gland and milk protein synthesis. Whether there are potential links among arginine, miRNA and casein synthesis in bovine mammary gland is uncertain. The objective of the present work was to detect the effects of arginine supplementation on the expression of miRNA associated with casein synthesis in mammary tissue and mammary epithelial cells (BMEC). The first study with bovine mammary epithelial cells (BMEC) focused on screening for miRNA candidates associated with the regulation of casein production by arginine. The BMEC were cultured with three different media, containing 0, 1.6 and 3.2 mM arginine, for 24 h. The expression of candidate miRNA was evaluated. Subsequently, in an in vivo study, 6 Chinese Holstein dairy cows with similar BW (mean ± SE) (512.0 ± 19.6 kg), parity (3), BCS (4.0) and DIM (190 ± 10.3 d) were randomly assigned to three experimental groups. The experimental cows received an infusion of casein, arginine (casein plus double the concentration of arginine in casein), and alanine (casein plus alanine, i.e., iso-nitrogenous to the arginine group) in a replicated 3 × 3 Latin square design with 22 d for each period (7 d for infusion and 15 d for washout). Mammary gland biopsies were obtained from each cow at the end of each infusion period. Results of the in vitro study showed differences between experimental groups and the control group for the expression of nine miRNA: miR-743a, miR-543, miR-101a, miR-760-3p, miR-1954, miR-712, miR-574-5p, miR-468 and miR-875-3p. The in vivo study showed that arginine infusion promoted milk protein content, casein yield and the expression of CSN1S1 and CSN1S2. Furthermore, the expression of miR-743a, miR-543, miR-101a, miR-760-3p, miR-1954, and miR-712 was also greater in response to arginine injection compared with the control or alanine group. Overall, results both in vivo and in vitro revealed that arginine might partly influence casein yield by altering the expression of 6 miRNAs (miR-743a, miR-543, miR-101a, miR-760-3p, miR-1954, and miR-712).

DNA POLYMERASE ACTIVITY IN MAMMARY GLAND OF VIRGIN MICE AFTER OVARIAN HORMONE TREATMENT

1971 ◽  
Vol 51 (2) ◽  
pp. 259-264 ◽  
Author(s):  
D. N. BANERJEE ◽  
M. R. BANERJEE ◽  
JANICE WAGNER
Keyword(s):  
Mammary Gland ◽  
Dna Polymerase ◽  
Hormone Treatment ◽  
Ovarian Hormones ◽  
Polymerase Activity ◽  
Mouse Mammary Gland ◽  
Supernatant Fraction ◽  
Mammary Tissue ◽  
Ovariectomized Mice

SUMMARY The effect of ovarian hormones on DNA polymerase activity in the mouse mammary gland was determined. The rate of [3H]thymidine triphosphate incorporation into DNA during incubation in vitro was used as a measure of DNA polymerase activity in the post-microsomal supernatant fraction of the mammary tissue. A negligible amount of DNA polymerase activity was present in the mammary tissue of ovariectomized mice which had no hormone treatment. Daily subcutaneous injections of 1 μg oestradiol-17β plus 1 mg progesterone induced a sixfold increase of DNA polymerase activity in the mammary tissue after two injections. A single intraperitoneal injection of the same dose also induced a similar rise of DNA polymerase activity and the effect was evident within hours after the treatment. The results provide evidence that stimulation of cellular biosynthesis by the growth-promoting ovarian hormones is associated with the activation of a specific enzyme involved in DNA replication.

In vitro analysis of the hormonal basis for the sexual dimorphism in the embryonic development of the mouse mammary gland

Development ◽  
1971 ◽  
Vol 25 (1) ◽  
pp. 141-153
Author(s):  
Klaus Kratochwil
Keyword(s):  
Mammary Gland ◽  
Sexual Dimorphism ◽  
Embryonic Development ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Female Type ◽  
Male Type ◽  
Endocrine Organs ◽  
Vitro Analysis

Factors underlying the sexual dimorphism in the embryonic development of mouse mammary glands were analysed in vitro and the following results were obtained: 1. Mammary gland rudiments of 13-day male embryos, explanted immediately before the onset of their regression, were perfectly capable of developing into female-type glands in vitro. Even some of the glands of 14-day male embryos, where the regression process had already begun, recovered after explantation and underwent female-type morphogenesis. 2. Combined explantation of 13-day testes with mammary rudiments of female embryos of 12–14 days gestation resulted in male-type regression of the glands. 3. The addition of testosterone to the culture medium caused a similar regression of explanted (female) mammary-gland rudiments. The minimal effective concentration of the hormone was 10−9m, or 0·00029 μg/ml. 4. Cultured mammary rudiments of 15-day female embryos were no longer responsive to the presence of testis explants. They failed to undergo regression and continued their development in vitro. From these results the following conclusions were drawn: (a) The sexual dimorphism in the embryonic development of mouse mammary glands is caused by their suppression in males and not by their stimulation in female embryos. (b) The androgenic hormones in male foetuses are solely responsible for the regression of the mammary rudiments. They exert their effect directly on the gland without the need for involvement of other endocrine organs. (c) The genetic sex of the gland itself has no influence on its developmental capacities as: (i) glands of male embryos are able to develop in the absence of androgens, and (ii) glands of female embryos undergo typical male-type regression in vitro when exposed to the presence of foetal testes or of testosterone.

scholarly journals Mouse mammary gland reconstitution with extrinsic gene-transferred mammary epithelial cells in vitro and in vivo

2008 ◽  
Vol 28 (3) ◽  
pp. 181-188
Author(s):  
Kazuharu Kai ◽  
Takatsune Shimizu ◽  
Eiji Sugihara ◽  
Yutaka Yamamoto ◽  
Hirotaka Iwase ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial

Characteristics of transport systems of L-alanine in mouse mammary gland and their regulation by lactogenic hormones: evidence for two broad spectrum systems

1999 ◽  
Vol 66 (3) ◽  
pp. 385-398 ◽  
Author(s):  
REKHA SHARMA ◽  
VINOD K. KANSAL
Keyword(s):  
Mammary Gland ◽  
Isobutyric Acid ◽  
Pregnant Mouse ◽  
Mouse Mammary Gland ◽  
Transport Systems ◽  
Mammary Tissue ◽  
System A ◽  
System L ◽  
Lactogenic Hormones

The characteristics of the transport systems of L-alanine in lactating mouse mammary gland and their regulation by lactogenic hormones have been studied. L-alanine uptake was mediated by three Na+-dependent and one Na+- independent systems. The 2-(methylamino)isobutyric acid-sensitive component of Na+-dependent uptake exhibited the usual characteristics of system A. Cl− dependency has been established for system A. The other two Na+-dependent systems, which we have named BCl−-dependent and BCl−-independent, are described for the first time. These are systems with broad specificity and were distinguished on the basis of inhibition analysis, Cl− dependency and the effect of preloading mammary tissue with amino acids. The Na+-independent route was identified as system L, which operates independent of Cl−. The A, L and BCl−-independent transport systems were upregulated in pregnant mouse mammary tissue cultured in vitro in the presence of lactogenic hormones (insulin plus cortisol plus prolactin). Insulin alone also upregulated systems A and L to some extent in pregnant mouse mammary tissue. BCl−-dependent activity was not detected in pregnant mouse mammary tissue and was not induced by lactogenic hormones in vitro.

The deletion of yeaJ gene facilitates Escherichia coli escape from immune recognition

2021 ◽  
Author(s):  
Xudong Wang ◽  
Xinguang Lin ◽  
Zhixin Wan ◽  
Shaohui Wang ◽  
Jiakun Zuo ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Innate Immunity ◽  
Mammary Gland ◽  
Mammary Epithelial Cells ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
Immune Recognition ◽  
E Coli

Mammary gland-derived Escherichia coli ( E. coli ) is an important pathogen causing dairy cow mastitis. Mammary gland mucosal immunity against infectious E. coli mainly depends on recognition of pathogen-associated molecular patterns by innate receptors. Stimulator of interferon (IFN) gene (STING) has recently been the dominant mediator in reacting to bacterial intrusion and preventing inflammatory disorders. In this study, we firstly proved that diguanylate cyclase YeaJ relieves mouse mammary gland pathological damage by changing E. coli phenotypic and host STING-dependent innate immunity response. YeaJ decreases mammary gland circular vacuoles, bleeding and degeneration in mice. In addition, YeaJ participates in STING-IRF3 signaling to regulate inflammation in vivo . While in vitro , YeaJ decreases damage to macrophages (RAW264.7) but not to mouse mammary epithelial cells (EpH4-Ev). Consistent with the results in mouse mammary gland, yeaJ significantly activates STING/TBK1/IRF3 pathway in RAW264.7 as well. In conclusion, the deletion of yeaJ gene facilitates E. coli NJ17 escape from STING-dependent innate immunity recognition in vitro and in vivo . This study highlights a novel role for YeaJ in E. coli infection, which provides a better understanding of host-bacteria interactions and potential prophylactic strategies for infections. IMPORTANCE E. coli is the etiological agent of environmental mastitis in dairy cows, which cause massive financial losses worldwide. However, the pathophysiological role of yeaJ in the interaction between E. coli and host remains unclear. We found that YeaJ significantly influences various biological characteristics and suppresses severe inflammatory response as well as greater damage. YeaJ alleviates damage to macrophages (RAW264.7) and mouse mammary gland. Moreover, these effects of YeaJ are achieved at least partial by mediating the STING-IRF3 signaling pathway. In conclusion, the deletion of yeaJ gene facilitates E. coli NJ17 escape from STING-dependent innate immunity recognition in vitro and in vivo. This study is the basis for further research to better understand host-bacteria interactions and provides potential prophylactic strategies for infections.

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