The plasminogen receptor,Plg‐RKT,is essential for mammary lobuloalveolar development and lactation

Implantation of excised bud-free ductal fragments (DUCTS), terminal end buds (TEBs), or alveolar buds (ABs) from virgin mammary glands of Wistar-Furth rats into interscapular fat pads of syngeneic female rats produces, after 16 weeks, complete ductal outgrowths including TEBs and ABs. Treatment of the recipient rats with perphenazine for 1 day or mating them after 12 weeks and then isolating the resultant outgrowths after 16 weeks produces significantly larger outgrowths than those from untreated hosts. The outgrowths consist of distended ducts and lobules or distended ducts and alveoli, respectively. Histochemical and immunocytochemical staining of the outgrowths with reagents that depict epithelial, myoepithelial, and lactating alveolar cells (peanut lectin alone, monoclonal and polyclonal antibodies to rat caseins) indicate similar cell compositions and arrangements for all outgrowths irrespective of their source; these are also similar to the mammary glands of the perphenazine-stimulated or lactating hosts. There is one major difference: the degree of staining of peanut lectin alone and the anti-caseins is greater for outgrowths produced by the ABs and TEBs than for those produced by the DUCTs. DUCT implants left for 1 year after cessation of lactation of the hosts are still stained appreciably by peanut lectin alone and by the anti-caseins, particularly the luminal secretions. Therefore, the complete morphogenetic and cell differentiating ability for generating mammary glands is present in bud-free ducts, but this ability can be enhanced in TEBs/ABs or abnormally expressed at ectopic sites.

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XIAP-deficiency leads to delayed lobuloalveolar development in the mammary gland

Cell Death and Differentiation ◽

10.1038/sj.cdd.4401524 ◽

2004 ◽

Vol 12 (1) ◽

pp. 87-90 ◽

Cited By ~ 47

Author(s):

M A Olayioye ◽

H Kaufmann ◽

M Pakusch ◽

D L Vaux ◽

G J Lindeman ◽

...

Keyword(s):

Mammary Gland ◽

Lobuloalveolar Development

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Temporally regulated overexpression of parathyroid hormone-related protein in the mammary gland reveals distinct fetal and pubertal phenotypes

Journal of Endocrinology ◽

10.1677/joe.0.1710403 ◽

2001 ◽

Vol 171 (3) ◽

pp. 403-416 ◽

Cited By ~ 35

Author(s):

ME Dunbar ◽

P Dann ◽

CW Brown ◽

J Van Houton ◽

B Dreyer ◽

...

Keyword(s):

Mammary Gland ◽

Parathyroid Hormone ◽

Transgenic Mice ◽

Mammary Development ◽

Related Protein ◽

Parathyroid Hormone Related Protein ◽

Epithelial Cell Apoptosis ◽

Ductal Elongation ◽

Ductal Branching ◽

Lobuloalveolar Development

We have previously demonstrated that overexpression of parathyroid hormone-related protein (PTHrP) in the mammary glands of transgenic mice results in defects in ductal elongation and branching during puberty and in lobuloalveolar development during pregnancy. In addition, we have shown that PTHrP is necessary for the formation of the initial ductal tree during embryonic mammary development. In order to examine the effect of varying the timing of PTHrP overexpression on mammary development, we created tetracycline-regulated, K14-tTA/Tet(O)-PTHrP double transgenic mice. In this report, we document that this 'tet-off' system directs transgene expression to the mammary gland and that it is fully repressed in the presence of tetracycline. Using these mice, we demonstrate that transient overexpression of PTHrP before birth causes defects in ductal branching during puberty and that overexpression of PTHrP during puberty decreases the rate of ductal elongation. Furthermore, we demonstrate that if PTHrP overexpression is initiated after ductal morphogenesis is completed, lobuloalveolar development is unaffected. Finally, we demonstrate that the impairment in ductal elongation caused by PTHrP is associated with an increase in the basal rate of epithelial cell apoptosis in terminal end buds and a failure to increase end bud cell proliferation and decrease apoptosis in response to estrogen and progesterone.

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The Epithelial Glucocorticoid Receptor Is Required for the Normal Timing of Cell Proliferation during Mammary Lobuloalveolar Development but Is Dispensable for Milk Production

Molecular Endocrinology ◽

10.1210/me.2004-0068 ◽

2005 ◽

Vol 19 (2) ◽

pp. 340-349 ◽

Cited By ~ 40

Author(s):

Tim M. Wintermantel ◽

Dagmar Bock ◽

Verena Fleig ◽

Erich F. Greiner ◽

Günther Schütz

Keyword(s):

Cell Proliferation ◽

Glucocorticoid Receptor ◽

Milk Production ◽

Lobuloalveolar Development

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Loss of the Heparan Sulfate Sulfotransferase, Ndst1, in Mammary Epithelial Cells Selectively Blocks Lobuloalveolar Development in Mice

PLoS ONE ◽

10.1371/journal.pone.0010691 ◽

2010 ◽

Vol 5 (5) ◽

pp. e10691 ◽

Cited By ~ 27

Author(s):

Brett E. Crawford ◽

Omai B. Garner ◽

Joseph R. Bishop ◽

David Y. Zhang ◽

Kevin T. Bush ◽

...

Keyword(s):

Epithelial Cells ◽

Heparan Sulfate ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Lobuloalveolar Development

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Disruption of Steroid and Prolactin Receptor Patterning in the Mammary Gland Correlates with a Block in Lobuloalveolar Development

Molecular Endocrinology ◽

10.1210/me.2002-0239 ◽

2002 ◽

Vol 16 (12) ◽

pp. 2675-2691 ◽

Cited By ~ 76

Author(s):

Sandra L. Grimm ◽

Tiffany N. Seagroves ◽

Elena B. Kabotyanski ◽

Russell C. Hovey ◽

Barbara K. Vonderhaar ◽

...

Keyword(s):

Cell Fate ◽

Binding Protein ◽

Prolactin Receptor ◽

Mammary Epithelium ◽

Mammary Epithelial ◽

Epidermal Differentiation ◽

Bzip Transcription Factor ◽

Mammary Tissue ◽

Critical Determinant ◽

Lobuloalveolar Development

Abstract Targeted deletion of the bZIP transcription factor, CCAAT/enhancer binding protein-β (C/EBPβ), was shown previously to result in aberrant ductal morphogenesis and decreased lobuloalveolar development, accompanied by an altered pattern of progesterone receptor (PR) expression. Here, similar changes in the level and pattern of prolactin receptor (PrlR) expression were observed while screening for differentially expressed genes in C/EBPβnull mice. PR patterning was also altered in PrlRnull mice, as well as in mammary tissue transplants from both PrlRnull and signal transducer and activator of transcription (Stat) 5a/b-deficient mice, with concomitant defects in hormone-induced proliferation. Down-regulation of PR and activation of Stat5 phosphorylation were seen after estrogen and progesterone treatment in both C/EBPβnull and wild-type mice, indicating that these signaling pathways were functional, despite the failure of steroid hormones to induce proliferation. IGF binding protein-5, IGF-II, and insulin receptor substrate-1 all displayed altered patterns and levels of expression in C/EBPβnull mice, suggestive of a change in the IGF signaling axis. In addition, small proline-rich protein (SPRR2A), a marker of epidermal differentiation, and keratin 6 were misexpressed in the mammary epithelium of C/EBPβnull mice. Together, these data suggest that C/EBPβ is a master regulator of mammary epithelial cell fate and that the correct spatial pattern of PR and PrlR expression is a critical determinant of hormone-regulated cell proliferation.

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The Neuropeptide Galanin Augments Lobuloalveolar Development

Journal of Biological Chemistry ◽

10.1074/jbc.m303746200 ◽

2003 ◽

Vol 278 (31) ◽

pp. 29145-29152 ◽

Cited By ~ 15

Author(s):

Matthew J. Naylor ◽

Erika Ginsburg ◽

Tiina P. Iismaa ◽

Barbara K. Vonderhaar ◽

David Wynick ◽

...

Keyword(s):

Lobuloalveolar Development

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Role of the ovaries in inducing mammogenesis in pregnant pigs

Journal of Endocrinology ◽

10.1677/joe.0.1180041 ◽

1988 ◽

Vol 118 (1) ◽

pp. 41-45 ◽

Cited By ~ 7

Author(s):

H. L. Buttle

Keyword(s):

Mammary Glands ◽

Corpora Lutea ◽

Lobuloalveolar Development

ABSTRACT Ovariectomy, but not removal of the corpora lutea, of gilts at mid-pregnancy delayed the onset of lobuloalveolar development in the mammary glands. Lactogenesis at the time of parturition was delayed by both ovariectomy and removal of the corpora lutea. J. Endocr. (1988) 118,41–45

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EXPERIMENTAL INDUCTION OF MAMMOGENESIS AND LACTOGENESIS IN THE DWARF MOUSE

Acta Endocrinologica ◽

10.1530/acta.0.0370161 ◽

1961 ◽

Vol 37 (2) ◽

pp. 161-175 ◽

Cited By ~ 3

Author(s):

Lillian E. Pissott ◽

Satyabrata Nandi

Keyword(s):

Mammary Gland ◽

Mammary Cancer ◽

Mammary Glands ◽

Pituitary Hormones ◽

Dwarf Mouse ◽

Alveolar Development ◽

Experimental Induction ◽

Pituitary Glands ◽

Dwarf Mice ◽

Lobuloalveolar Development

ABSTRACT The response of the mammary glands to exogenous hormones was studied in genetically hormone-deficient intact dwarf mice. Some ductal growth was observed after the administration of thyroxin alone or in combination with ovarian and adrenocortical steroids. Combinations of steroids without thyroxin did not induce appreciable growth of the mammary gland. Addition of pituitary somatotrophin or mammotrophin to the combinations containing steroids and thyroxin resulted in further ductal stimulation and some alveolar development. Lactogenesis could be induced in the mammary glands of dwarf mice by injecting an initial hormone combination which would result in lobuloalveolar development and following this by a combination of pituitary and adrenocortical hormones which induces milk secretion. The most effective treatment for the induction of lactogenesis was oestradiol-17β + progesterone + cortisol acetate + mammotrophin + somatotrophin + thyroxin followed by mammotrophin + somatotrophin + cortisol acetate. Mammotrophin and somatotrophin were observed to be equally effective in inducing mammogenesis and lactogenesis in the dwarfs. The response of the mammary gland of the dwarf mouse to exogenous pituitary hormones (excluding thyroxin-containing combinations) seems similar to that of hypophysectomized mice of various strains in which the mammary cancer incidence is high in virgin as well as breeding females. The significant growth of mammary glands as a result of thyroxin treatment alone and the increased mammogenic effect of thyroxin-containing steroid combinations suggest that thyroxin promotes manufacture and/or release of somatotrophin and gonadotrophin from the anterior pituitary glands of dwarf mice.

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