scholarly journals Progesterone receptors in normal mammary gland: receptor modulations in relation to differentiation.

1980 ◽  
Vol 86 (3) ◽  
pp. 730-737 ◽  
Author(s):  
S Z Haslam ◽  
G Shyamala
Keyword(s):  
Mammary Gland ◽  
Progesterone Receptors ◽  
Mammary Development ◽  
Mammary Tissue ◽  
Normal Mammary Gland ◽  
Negative Effect ◽  
Pregnancy And Lactation ◽  
Two Stages ◽  
Mammary Gland Differentiation

The biological basis for the observed modulation in cytoplasmic progesterone receptors (PgR) of normal mammary gland occurring during mammary development was investigated. Specifically, the relative roles of hormones vs. differentiation on (a) the decrease in PgR concentration during pregnancy and lactation and (b) the loss of mammary responsiveness to estrogen during lactation were examined. PgR were measured using the synthetic progestin, R5020, as the ligand. The hormones estrogen and progesterone were tested in vivo for their effect of PgR concentration. Mammary gland differentiation was assessed morphologically and by measuring enzymatically active alpha-lactalbumin. These studies show that there is a stepwise decrease in PgR that occurs in two stages. The first decrease is completed by day 12 of pregnancy and the second decrease occurs only after parturition. There appears to be a hormonal basis for the first decrease and it appears to be caused by the negative effect of progesterone on estrogen-mediated increase in PgR. In direct contrast, the absence of PgR during lactation and the mammary tissue insensitivity to estrogenic stimulation of PgR were not related to the hormonal milieu of lactation but were directly related to the secretory state of the mammary gland and lactation per se.

scholarly journals Developmental regulation of Bcl-2 family protein expression in the involuting mammary gland

1999 ◽  
Vol 112 (11) ◽  
pp. 1771-1783 ◽  
Author(s):  
A.D. Metcalfe ◽  
A. Gilmore ◽  
T. Klinowska ◽  
J. Oliver ◽  
A.J. Valentijn ◽  
...  
Keyword(s):  
Cell Death ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
De Novo ◽  
Mammary Epithelial Cells ◽  
Expression Profiles ◽  
Mammary Epithelial ◽  
Mammary Tissue ◽  
Pregnancy And Lactation

Epithelial cells within the mammary gland undergo developmental programmes of proliferation and apoptosis during the pregnancy cycle. After weaning, secretory epithelial cells are removed by apoptosis. To determine whether members of the Bcl-2 gene family could be involved in regulating this process, we have examined whether changes in their expression occur during this developmental apoptotic program in vivo. Bax and Bcl-x were evenly expressed throughout development. However, expression of Bak and Bad was increased during late pregnancy and lactation, and the proteins were present during the time of maximal apoptotic involution. Thereafter, their levels declined. In contrast, Bcl-w was expressed in pregnancy and lactation but was downregulated at the onset of apoptosis. Bcl-2 was not detected in lactating or early involuting mammary gland. Thus, the pro-apoptotic proteins Bax, Bak and Bad, as well as the death-suppressors Bcl-x, Bcl-2 and Bcl-w, are synthesised in mouse mammary gland, and dynamic changes in the expression profiles of these proteins occurs during development. To determine if changes in Bak and Bcl-w expression could regulate mammary apoptosis, their effect on cultured mouse mammary epithelial cells was examined in transient transfection assays. Enforced expression of Bak induced rapid mammary apoptosis, which could be suppressed by coexpression of Bcl-w. In extracts of mammary tissue in vivo, Bak heterodimerized with Bcl-x whereas Bax associated with Bcl-w, but Bak/Bcl-w heterodimers were not detected. Thus, Bak and Bcl-w may regulate cell death through independent pathways. These results support a model in which mammary epithelial cells are primed for apoptosis during the transition from pregnancy to lactation by de novo expression of the death effectors Bak and Bad. It is suggested that these proteins are prevented from triggering apoptosis by anti-apoptotic Bcl-2 family proteins until involution, when the levels of Bcl-w decline. Our study provides evidence that regulated changes in the expression of cell death genes may contribute to the developmental control of mammary apoptosis.

Proteinases of the mammary gland: developmental regulation in vivo and vectorial secretion in culture

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 439-449 ◽  
Author(s):  
R.S. Talhouk ◽  
J.R. Chin ◽  
E.N. Unemori ◽  
Z. Werb ◽  
M.J. Bissell
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Cell Function ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
The Other ◽  
Mammary Tissue ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Extracts

The extracellular matrix (ECM) is an important regulator of mammary epithelial cell function both in vivo and in culture. Substantial remodeling of ECM accompanies the structural changes in the mammary gland during gestation, lactation and involution. However, little is known about the nature of the enzymes and the processes involved. We have characterized and studied the regulation of cell-associated and secreted mammary gland proteinases active at neutral pH that may be involved in degradation of the ECM during the different stages of mammary development. Mammary tissue extracts from virgin and pregnant CD-1 mice resolved by zymography contained three major proteinases of 60K (K = 10(3) Mr), 68K and 70K that degraded denatured collagen. These three gelatinases were completely inhibited by the tissue inhibitor of metalloproteinases. Proteolytic activity was lowest during lactation especially for the 60K gelatinase which was shown to be the activated form of the 68K gelatinase. The activated 60K form decreased prior to parturition but increased markedly after the first two days of involution. An additional gelatin-degrading proteinase of 130K was expressed during the first three days of involution and differed from the other gelatinases by its lack of inhibition by the tissue inhibitor of metalloproteinases. The activity of the casein-degrading proteinases was lowest during lactation. Three caseinolytic activities were detected in mammary tissue extracts. A novel 26K cell-associated caseinase—a serine arginine-esterase—was modulated at different stages of mammary development. The other caseinases, at 92K and a larger than 100K, were not developmentally regulated. To find out which cell type produced the proteinases in the mammary gland, we isolated and cultured mouse mammary epithelial cells. Cells cultured on different substrata produced the full spectrum of gelatinases and caseinases seen in the whole gland thus implicating the epithelial cells as a major source of these enzymes. Analysis of proteinases secreted by cells grown on a reconstituted basement membrane showed that gelatinases were secreted preferentially in the direction of the basement membrane. The temporal pattern of expression of these proteinases and the basal secretion of gelatinases by epithelial cells suggest their involvement in the remodelling of the extracellular matrix during the different stages of mammary development and thus modulation of mammary cell function.

Suppression of ovarian secretions before puberty strongly affects mammogenesis in the goat

2012 ◽  
Vol 79 (2) ◽  
pp. 157-167 ◽  
Author(s):  
Lucile Yart ◽  
Laurence Finot ◽  
Pierre-Guy Marnet ◽  
Frédéric Dessauge
Keyword(s):  
Mammary Gland ◽  
Progesterone Receptors ◽  
Antigen Expression ◽  
Mammary Glands ◽  
Cell Number ◽  
Mammary Development ◽  
Border Region ◽  
Nuclear Antigen ◽  
Mammary Tissue ◽  
Pcr Analysis

The objective of this study was to provide insight into the biological mechanisms underlying mammary development and the role of the ovaries in prepubertal caprine mammogenesis using a serial ovariectomy approach. Young Alpine goats were ovariectomized (Ovx) or sham-operated (Int) at three periods before puberty (G1=1 month, G2=2 month and G3=3 months of age) and one after puberty (G7=7 months of age). The goats were slaughtered at 9 months of age and mammary glands were removed. Ovariectomy performed at 1, 2 and 3 months of age caused a 50% reduction in DNA concentration, in mammary tissue taken from the parenchyma-stroma border region. Morphological analysis of mammary tissue sections indicated that the parenchymal structures of Ovx goats were negatively affected by ovariectomy. Goats ovariectomized before 2 months of age (Ovx-1 and Ovx-2) showed a significant decrease in the percent of cells proliferating in mammary glands of 9-month old goats (proliferating cell nuclear antigen expression and antigen Ki67-positive cell number). Also, goats ovariectomized at 1 and 2 months of age had reduced matrix metalloprotease 2 activity at 9 months of age. E-cadherin was strongly decreased in goats ovariectomized before 2 months of age (80 and 85% in Ovx-1 and Ovx-2 goats, respectively). Quantitative PCR analysis of transcripts encoding for oestrogen (ERα) and progesterone receptors (PR) and immunodetection of ERα showed that ovariectomy at 1 and 2 months of age strongly inhibited the transcription of ERα and PR in the mammary gland. We conclude that ovariectomy before 3 months of age markedly impaired parenchymal development. These findings suggest that prepubertal mammogenesis in goats depends on the ovaries to initiate mammary epithelial cell proliferation and mammary gland remodelling.

scholarly journals Reproductive tissue selective actions of progesterone receptors

Reproduction ◽  
2004 ◽  
Vol 128 (2) ◽  
pp. 139-146 ◽  
Author(s):  
Biserka Mulac-Jericevic ◽  
Orla M Conneely
Keyword(s):  
Mammary Gland ◽  
Target Genes ◽  
Progesterone Receptors ◽  
Normal Mammary Gland ◽  
Female Reproduction ◽  
Biological Responses ◽  
Gland Morphogenesis ◽  
The Individual

The steroid hormone, progesterone, plays a central coordinate role in diverse events associated with female reproduction. In humans and other vertebrates, the biological activity of progesterone is mediated by modulation of the transcriptional activity of two progesterone receptors, PR-A and PR-B. These receptors arise from the same gene and exhibit both overlapping and distinct transcriptional activitiesin vitro. To delineate the individual roles of PR-A and PR-Bin vivo, we have generated mouse models in which expression of a single PR isoform has been ablated. Analysis of the reproductive phenotypes of these mice has indicated that PR-A and PR-B mediate mostly distinct but partially overlapping reproductive responses to progesterone. While selective ablation of the PR-A protein (PR-A knockout mice, PRAKO mice) shows normal mammary gland response to progesterone but severe uterine hyperplasia and ovarian abnormalities, ablation of PR-B protein (PRBKO mice) does not affect biological responses of the ovary or uterus to progesterone but results in reduced pregnancy-associated mammary gland morphogenesis. The distinct tissue-specific reproductive responses to progesterone exhibited by these isoforms are due to regulation of distinct subsets of progesterone-dependent target genes by the individual PR isoforms. This review will summarize our current understanding of the selective contribution of PR isoforms to the cellular and molecular actions of progesterone in reproductive tissues.

scholarly journals Loss of glutaredoxin 3 impedes mammary lobuloalveolar development during pregnancy and lactation

2017 ◽  
Vol 312 (3) ◽  
pp. E136-E149 ◽  
Author(s):  
Khanh Pham ◽  
Jie Dong ◽  
Xiqian Jiang ◽  
Ying Qu ◽  
Han Yu ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Redox Homeostasis ◽  
Physiological Role ◽  
Cell Types ◽  
Normal Mammary Gland ◽  
Pregnancy And Lactation ◽  
Gland Development ◽  
Lobuloalveolar Development

Mammalian glutaredoxin 3 (Grx3) has been shown to be important for regulating cellular redox homeostasis in the cell. Our previous studies indicate that Grx3 is significantly overexpressed in various human cancers including breast cancer and demonstrate that Grx3 controls cancer cell growth and invasion by regulating reactive oxygen species (ROS) and NF-κB signaling pathways. However, it remains to be determined whether Grx3 is required for normal mammary gland development and how it contributes to epithelial cell proliferation and differentiation in vivo. In the present study, we examined Grx3 expression in different cell types within the developing mouse mammary gland (MG) and found enhanced expression of Grx3 at pregnancy and lactation stages. To assess the physiological role of Grx3 in MG, we generated the mutant mice in which Grx3 was deleted specifically in mammary epithelial cells (MECs). Although the reduction of Grx3 expression had only minimal effects on mammary ductal development in virgin mice, it did reduce alveolar density during pregnancy and lactation. The impairment of lobuloalveolar development was associated with high levels of ROS accumulation and reduced expression of milk protein genes. In addition, proliferative gene expression was significantly suppressed with proliferation defects occurring in knockout MECs during alveolar development compared with wild-type controls. Therefore, our findings suggest that Grx3 is a key regulator of ROS in vivo and is involved in pregnancy-dependent mammary gland development and secretory activation through modulating cellular ROS.

scholarly journals Regulation of lipogenic capacity in lactating rats

1982 ◽  
Vol 208 (3) ◽  
pp. 611-618 ◽  
Author(s):  
M R Grigor ◽  
A Geursen ◽  
M J Sneyd ◽  
S M Warren
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Specific Activity ◽  
Mammary Glands ◽  
Lipogenic Enzymes ◽  
Pregnancy And Lactation ◽  
Specific Activities

1. The rate of mammary-gland lipogenesis measured in vivo from 3H2O was suppressed after decreasing the milk demand by decreasing the number of pups from ten to two or three, as well as by giving diets containing lipid [Grigor & Warren (1980) Biochem. J. 188, 61-65]. 2. The specific activities of the lipogenic enzymes fatty acid synthase, glucose 6-phosphate dehydrogenase and ‘malic’ enzyme increased between 6- and 10-fold in the mammary gland and between 2- and 3-fold in the livers during the first 10 days of lactation. The increases in specific activity coupled with the doubling of liver mass which occurred during pregnancy and lactation resulted in considerable differences in total liver activities when compared with virgin animals. 3. Although consumption of a diet containing 20% peanut oil suppressed the activities of the three lipogenic enzymes in the livers, only the ‘malic’ enzyme was affected in the mammary glands. 4. In contrast, decreased milk demand did not affect the specific activities of any of the liver enzymes, whereas it resulted in suppression of all three lipogenic enzymes of the mammary glands. There was no effect on either the cytoplasmic malate dehydrogenase or the lactate dehydrogenase of the mammary gland. 5. In all the experiments performed, the activity of the fatty acid synthase correlated with the amount of material precipitated by the rabbit antibody raised against rat fatty acid synthase.

scholarly journals Diet and expression of estrogen alpha and progesterone receptors in the normal mammary gland

2008 ◽  
Vol 20 (5) ◽  
pp. 601-607
Author(s):  
Pagona Lagiou ◽  
Evangelia Samoli ◽  
Areti Lagiou ◽  
Christina Georgila ◽  
Pantelina Zourna ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Progesterone Receptors ◽  
Normal Mammary Gland

scholarly journals Progesterone Receptor Isoforms A and B: Temporal and Spatial Differences in Expression during Murine Mammary Gland Development

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3577-3588 ◽  
Author(s):  
Mark D. Aupperlee ◽  
Kyle T. Smith ◽  
Anastasia Kariagina ◽  
Sandra Z. Haslam
Keyword(s):  
Mammary Gland ◽  
Progesterone Receptor ◽  
Cyclin D1 ◽  
Mammary Gland Development ◽  
Minor Role ◽  
Normal Mammary Gland ◽  
Temporal Separation ◽  
Stage Of Development ◽  
Gland Development

Abstract Progesterone is a potent mitogen in the mammary gland. Based on studies using cells and animals engineered to express progesterone receptor (PR) isoforms A or B, PRA and PRB are believed to have different functions. Using an immunohistochemical approach with antibodies specific for PRA only or PRB only, we show that PRA and PRB expression in mammary epithelial cells is temporally and spatially separated during normal mammary gland development in the BALB/c mouse. In the virgin mammary gland when ductal development is active, the only PR protein isoform expressed was PRA. PRA levels were significantly lower during pregnancy, suggesting a minor role at this stage of development. PRB was abundantly expressed only during pregnancy, during alveologenesis. PRA and PRB colocalization occurred in only a small percentage of cells. During pregnancy there was extensive colocalization of PRB with 5-bromo-2′-deoxyuridine (BrdU) and cyclin D1; 95% of BrdU-positive cells and 83% of cyclin D1-positive cells expressed PRB. No colocalization of PRA with either BrdU or cyclin D1 was observed at pregnancy. In the virgin gland, PRA colocalization with BrdU or cyclin D1 was low; only 27% of BrdU-positive cells and 4% of cyclin D1-positive cells expressed PRA. The implication of these findings is that different actions of progesterone are mediated in PRB positive vs. PRA-positive cells in vivo. The spatial and temporal separation of PR isoform expression in mouse mammary gland provides a unique opportunity to determine the specific functions of PRA vs. PRB in vivo.

In-vivo magnetic resonance imaging studies of mammogenesis in non-pregnant goats treated with exogenous steroids

1991 ◽  
Vol 58 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Paul A. Fowler ◽  
Christopher H. Knight ◽  
Margaret A. Foster
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Maximum Size ◽  
Mammary Development ◽  
Mammary Tissue ◽  
Secretory Cells ◽  
Resonance Imaging ◽  
Secretion Efficiency ◽  
Cessation Of Treatment

SummaryMammogenesis and lactation were induced in five multiparous, non-pregnant goats by treatment with oestrogen and progesterone for 11 d, followed by dexamethasone for 3 d. Reserpine was administered during the last 5 d. All five goats lactated, although milk yield was less than had been achieved in previous natural lactations. Mammary development was assessed in vivo, using magnetic resonance imaging. Although parenchyma volume increased by more than 6-fold overall, only 25% of this increase occurred during steroid treatment. Most development took place after the cessation of treatment, when milking commenced. Maximum size was not achieved until week 8 of the induced lactation, and was only 70% of normal parenchyma volume. After 18 weeks lactation the activities of three key milk synthetic enzymes were very similar to values previously found in natural lactations, and secretion efficiency (milk production per unit volume of parenchyma) was also similar to that of natural lactations. We conclude that the lower than normal milk yields were associated with incomplete proliferation of mammary tissue, rather than inadequate differentiation of individual secretory cells.

Mammary gland biopsy does not affect lactation performance in sows

2007 ◽  
Vol 87 (2) ◽  
pp. 281-284 ◽  
Author(s):  
R. N. Kirkwood ◽  
J. Pérez Laspiur ◽  
N. K. Ames ◽  
J. B. Moore ◽  
A. Cegielski ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Feed Intake ◽  
Somatic Cell Count ◽  
Average Daily Gain ◽  
Mammary Tissue ◽  
Molecular Characteristics ◽  
Lactation Performance ◽  
Voluntary Feed Intake ◽  
Daily Gain

To determine morphological and molecular characteristics of porcine mammary tissue in vivo, mammary tissue was collected from 18 sows at 3 to 6 d of lactation and 17 to 19 d of lactation using a biopsy technique. The success of the technique was determined by monitoring lactation performance, as evidenced by sow rectal temperature, voluntary feed intake, milk somatic cell count, and piglet average daily gain. Up to 1.7 g of mammary tissue was collected at each biopsy without decreasing sow feed intake or piglet growth. Key words: Biopsy, mammary gland, lactation, sow

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