Uteroplacental insufficiency alters the mammary gland response to lactogenic hormones in vitro

2008 ◽  
Vol 20 (4) ◽  
pp. 460 ◽  
Author(s):  
Rachael O'Dowd ◽  
Mary E. Wlodek ◽  
Kevin R. Nicholas
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Postnatal Growth ◽  
Mammary Development ◽  
Mammary Tissue ◽  
Sham Surgery ◽  
Uterine Vessel ◽  
Lactogenic Hormones ◽  
Vessel Ligation

Adequate mammary development and coordinated actions of lactogenic hormones are essential for the initiation of lactation. Pregnancies compromised by uteroplacental insufficiency impair mammary development and lactation, further slowing postnatal growth. It is not known whether the initiation of lactation or galactopoesis is compromised. Uteroplacental insufficiency induced in rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on Day 18 of gestation preceded collection of mammary tissue on Day 20 of pregnancy. Mammary explants were cultured with combinations of insulin, cortisol and prolactin and analysed for α-lactalbumin and β-casein gene expression. Mammary tissue from late pregnant Restricted rats had elevated α-lactalbumin, but not β-casein, mRNA, which is consistent with premature lactogenesis resulting from an early decline in peripheral maternal progesterone. Explants from Restricted rats were more responsive to hormone stimulation after 3 days in culture, indicating that compromised galactopoesis, not lactogenesis, most likely leads to the reduced growth of suckled pups.

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.

Hormone-dependent milk protein gene expression in bovine mammary explants from biopsies at different stages of pregnancy

2004 ◽  
Vol 71 (2) ◽  
pp. 135-140 ◽  
Author(s):  
Paul A Sheehy ◽  
James J Della-Vedova ◽  
Kevin R Nicholas ◽  
Peter C Wynn
Keyword(s):  
Gene Expression ◽  
Milk Protein ◽  
Protein Gene ◽  
Bovine Milk ◽  
Mammary Tissue ◽  
Endocrine Regulation ◽  
Surgical Biopsy ◽  
Milk Protein Gene ◽  
Milk Protein Gene Expression

A method for the collection of mammary biopsies developed previously was refined and used to study the endocrine regulation of bovine milk protein gene expression. Our surgical biopsy method used real-time ultrasound imaging and epidural analgesia to enable recovery of a sufficient quantity of mammary tissue from late-pregnant dairy cows for explant culture in vitro. The time of biopsy was critical for prolactin-dependent induction of milk protein gene expression in mammary explants, as only mammary tissue from cows nearing 30 d prepartum was hormone-responsive. This suggests that during the later stages of pregnancy a change in the responsiveness of milk protein gene expression to endocrine stimuli occurred in preparation for lactation. This may relate to the diminution of a putative population of undifferentiated cells that were still responsive to prolactin. Alternatively, the metabolic activity of the tissue had increased to the level whereby the response of the tissue was no longer assessable using this model in vitro.

scholarly journals Characterization and biological activity of relaxin in porcine milk

Reproduction ◽  
2011 ◽  
Vol 141 (3) ◽  
pp. 373-380 ◽  
Author(s):  
Amy-Lynn Frankshun ◽  
Teh-Yuan Ho ◽  
David C Reimer ◽  
Joseph Chen ◽  
Salamia Lasano ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Milk Proteins ◽  
Immunoblot Analysis ◽  
Mammary Tissue ◽  
Early Lactation ◽  
Maternal Circulation ◽  
A Site ◽  
Porcine Milk ◽  
Primary Form

A lactocrine mechanism for delivery of maternally derived relaxin (RLX) into the neonatal circulation as a consequence of nursing was proposed for the pig. Immunoreactive RLX was detected in colostrum and in the serum of newborn pigs only if they were allowed to nurse. Milk-borne RLX concentrations are highest during early lactation (9–19 ng/ml), declining to <2 ng/ml by postnatal day 14. Whether milk-borne RLX is bioactive is unknown. Evidence that RLX concentrations in milk are higher than in maternal circulation in several species suggests the mammary gland as a site of local RLX production. It is unknown whether the porcine mammary gland is a source of RLX. Therefore, objectives were to evaluate RLX bioactivity in porcine milk during the first 2 weeks of lactation, identify the form of RLX in porcine milk, and determine whether mammary tissue from early lactation is a source of milk-borne RLX. Milk RLX bioactivity was determined using anin vitrobioassay in which cAMP production by human embryonic kidney (HEK293T) cells transfected with the human RLX receptor (RXFP1) was measured. RLX bioactivity was highest at lactation day (LD) 0, decreasing to undetectable levels by LD 4. Immunoblot analysis of milk proteins revealed an 18 kDa band, indicating proRLX as the primary form of RLX in porcine milk. ProRLX protein and transcripts were detected in porcine mammary tissue on LD 0 and 7. Results support the lactocrine hypothesis by defining the nature and a potential source for bioactive proRLX in porcine colostrum/milk.

Nuclear targeting of stanniocalcin to mammary gland alveolar cells during pregnancy and lactation

2005 ◽  
Vol 289 (4) ◽  
pp. E634-E642 ◽  
Author(s):  
Craig P. Hasilo ◽  
Christopher R. McCudden ◽  
J. Ryan J. Gillespie ◽  
Kathi A. James ◽  
Edward R. Hirvi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Molecular Mass ◽  
Chemical Reduction ◽  
Mammary Tissue ◽  
Nuclear Targeting ◽  
Alveolar Cells ◽  
Hormone Production ◽  
Pregnant Rats ◽  
Pregnancy And Lactation

In most mammalian tissues, the stanniocalcin-1 gene (STC-1) produces a 50-kDa polypeptide hormone known as STC50. Within the ovaries, however, the STC-1 gene generates three higher-molecular-mass variants known as big STC. Big STC is targeted locally to corpus luteal cells to block progesterone release. During pregnancy and lactation, however, ovarian big STC production increases markedly, and the hormone is released into the serum. During lactation, this increase in hormone production is dependent on a suckling stimulus, suggesting that ovarian big STC may have regulatory effects on the lactating mammary gland. In this report, we have addressed this possibility. Our results revealed that virgin mammary tissue contained large numbers of membrane- and mitochondrial-associated STC receptors. However, as pregnancy progressed into lactation, there was a decline in receptor densities on both organelles and a corresponding rise in nuclear receptor density, most of which were on milk-producing, alveolar cells. This was accompanied by nuclear sequestration of the ligand. Sequestered STC resolved as one ∼135-kDa band in the native state and therefore had the appearance of a big STC variant. However, chemical reduction collapsed this one band into six closely spaced, lower-molecular-mass species (28–41 kDa). Mammary gland STC production also underwent a dramatic shift during pregnancy and lactation. High levels of STC gene expression were observed in mammary tissue from virgin and pregnant rats. However, gene expression then fell to nearly undetectable levels during lactation, coinciding with the rise in nuclear targeting. These findings have thus shown that the mammary glands are indeed targeted by STC, even in the virgin state. They have further shown that there are marked changes in this targeting pathway during pregnancy and lactation, accompanied by a switch in ligand source (endogenous to exogenous). They also represent the first example of nuclear targeting by STC.

scholarly journals The expression of the IGF family and GH receptor in the bovine mammary gland

2001 ◽  
Vol 168 (1) ◽  
pp. 39-48 ◽  
Author(s):  
A Plath-Gabler ◽  
C Gabler ◽  
F Sinowatz ◽  
B Berisha ◽  
D Schams
Keyword(s):  
Mammary Gland ◽  
Binding Proteins ◽  
Mammary Development ◽  
Mammary Tissue ◽  
Bovine Mammary Gland ◽  
Igf Binding Proteins ◽  
Gh Receptor ◽  
Igf I ◽  
Temporal Expressions ◽  
Igfbp 3

To study the involvement of the IGFs in mammary development and lactation of the cow, the temporal expressions of IGF-I and -II, its receptor type 1 (IGFR-1), IGF-binding proteins (IGFBPs)-1 to -6 and GH receptor (GHR) mRNA were examined. This was carried out for different stages of mammogenesis, lactogenesis, galactopoiesis and involution in the bovine mammary gland of 26 animals. Furthermore, IGF-I was localised by immunohistochemistry. The highest mRNA concentrations for IGF-I were detected in the mammary tissue of late pregnant heifers (days 255-272) and significantly lower expression was detected during lactogenesis and galactopoiesis. Immunohistochemistry of IGF-I revealed only a weak staining in the epithelium of the ducts during mammogenesis. The epithelium of the alveoli were negative during mammogenesis, lactogenesis and galactopoiesis but displayed distinct IGF-I activity during involution. In the stroma a distinct staining of the cytoplasm of adipocytes and of vascular smooth muscle cells was observed. A certain percentage of fibroblasts (usually 20-30%) were also immunopositive. In contrast, highest expression for IGFR-1 was detected during galactopoiesis and involution. The lowest mRNA concentration for IGFR-1 was found during pregnancy (days 194-213). In general, the expression of IGF-II was not regulated during mammogenesis and lactation, but decreased during involution. The mRNA for the six binding proteins was detected in the bovine mammary gland. The dominant binding proteins were IGFBP-3 and -5. The highest expression of IGFBP-3 was observed during mid-pregnancy and the lowest during late lactation, involution and in non-pregnant heifers. The mRNA for IGFBP-5 increased during late mammogenesis and lactogenesis followed by a decrease thereafter. In general, the mRNA concentrations for IGFBP-2, -4 and -6 were barely detectable during all stages. In contrast, the expression for IGFBP-1 was upregulated in the mammary gland of virgin heifers and increased around the onset of lactation. mRNA for GHR was found during all stages examined without outstanding fluctuations. In conclusion, locally produced IGF-I and -II may mediate mammogenesis. The high mammary IGFR-1 mRNA during lactation suggests a role for peripheral IGF-I in maintenance of lactation. The role of IGFBPs in the mammary gland needs further evaluation.

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.

Effect of exogenous bovine growth hormone and ovariectomy on prepubertal mammary growth, serum hormones and acute in-vitro proliferative response of mammary explants from Holstein heifers

1993 ◽  
Vol 139 (1) ◽  
pp. 19-26 ◽  
Author(s):  
S. Purup ◽  
K. Sejrsen ◽  
J. Foldager ◽  
R. M. Akers
Keyword(s):  
Mammary Gland ◽  
Growth Response ◽  
Mammary Development ◽  
Tissue Growth ◽  
Epithelial Tissue ◽  
Holstein Friesian ◽  
Serum Hormone ◽  
Term Administration

ABSTRACT Sixteen prepubertal Holstein Friesian heifers were used to study the effect of long-term administration of bovine GH (bGH) on mammary development in intact and ovariectomized heifers. Eight heifers were ovariectomized at 2·5 months of age. Four intact and four ovariectomized heifers received subcutaneous injection of bGH (15 mg/day) for 15 weeks starting at 176 ± 3 days of age (147 ± 3 kg body weight), while the remaining eight heifers received an equal volume of excipient. Blood samples were collected weekly from 2 months of age. Heifers were slaughtered on the day after the last injection of bGH or excipient. Mammary gland development was quantified by dissection, chemical analysis and computer tomographic scanning. Mammary growth response at the time of slaughter was examined in cultures with explants prepared from parenchyma. Histological and histoautoradiographic studies with explants were performed. Treatment with bGH resulted in a significantly (P<0·05) smaller mammary gland because of a reduced amount of extraparenchymal tissue. Ovariectomy markedly reduced the amount of parenchymal tissue. Growth response in mammary explants showed no treatment differences, suggesting that the decreased amount of parenchyma in ovariectomized heifers was caused by a decrease in mammary cell proliferation occurring some time prior to slaughter. The histological composition of mammary parenchyma was not changed by bGH treatment. However, ovariectomy resulted in less epithelial tissue (P<0·001) and lumen (P<0·05) and more stroma (P< 0·001), expressed as percentage tissue area. Serum hormone concentrations of bGH and insulin-like growth factor-I (IGF-I) were increased by bGH treatment in both intact and ovariectomized heifers. However, despite the fact that mammary growth in ovariectomized heifers was eradicated, the serum concentration of oestradiol was only decreased by one-third compared with intact heifers. The study therefore confirms the importance of ovarian secretions for mammary growth and development in prepubertal heifers. However, the results give no clear evidence of an interaction between ovarian secretions and GH on the regulation of the development of the mammary parenchyma in heifers. Journal of Endocrinology (1993) 139, 19–26

scholarly journals Studies of the regulation of the mouse carboxyl ester lipase gene in mammary gland

1998 ◽  
Vol 336 (3) ◽  
pp. 577-585 ◽  
Author(s):  
Marie KANNIUS-JANSON ◽  
Ulf LIDBERG ◽  
Kåre HULTÉN ◽  
Amel GRITLI-LINDE ◽  
Gunnar BJURSELL ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Gene Promoter ◽  
Positive Element ◽  
Lipase Gene ◽  
Lactating Mammary Gland ◽  
Lactogenic Hormones ◽  
Nuclear Factor 1 ◽  
Promoter Studies ◽  
Mammary Gland Differentiation

The lactating mammary gland and pancreas of mouse constitute the main tissues for synthesis and secretion of a bile-salt-stimulated lipase called carboxyl ester lipase (CEL). In this paper we have analysed the endogenous CEL gene expression in mammary gland. It is shown that the gene is expressed at day 14 of pregnancy, which is synchronous with that of the whey acidic protein (WAP) gene. Even though the CEL and WAP genes are induced at the same time during mammary gland differentiation, their regulation is different with respect to dependence on lactogenic hormones. The high induction of the WAP gene expression due to the activation of signal transducer and activator of transcription (STAT)5 by prolactin has not been observed for the CEL gene, even though it has been demonstrated that both STAT5 isoforms interact with one of the γ-interferon activation sequence sites in the promoter of the CEL gene. Hence we have demonstrated that the prolactin/STAT5 signal is not involved in a general and significant activation of ‘milk genes ’. Instead of a direct effect of the lactogenic hormones, the up-regulation of the CEL gene is correlated with an increase in the number of differentiated epithelial cells. Furthermore, promoter studies using the mammary-gland-derived cell line, HC11, show that a major positive element in the CEL gene promoter interacts with a member(s) of the CCAAT-binding transcription factor/nuclear factor 1 family, binding to a palindromic site. Binding of this factor(s) is important for the tissue-specific activation of the CEL gene in the mammary gland, because no activation by this factor(s) was seen in cells of pancreatic origin.

Identification of estrogen-responsive genes in the parenchyma and fat pad of the bovine mammary gland by microarray analysis

2006 ◽  
Vol 27 (1) ◽  
pp. 42-53 ◽  
Author(s):  
Robert W. Li ◽  
Matthew J. Meyer ◽  
Curtis. P. Van Tassell ◽  
Tad S. Sonstegard ◽  
Erin E. Connor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Bos Taurus ◽  
Expression Patterns ◽  
Mammary Development ◽  
Bovine Mammary Gland ◽  
Fat Pad ◽  
Promoter Regions ◽  
Significance Level ◽  
Consensus Sequences

Identification of estrogen-responsive genes is an essential step toward understanding mechanisms of estrogen action during mammary gland development. To identify these genes, 16 prepubertal heifers were used in a 2 × 2 factorial experiment, with ovarian status (intact or ovariectomized) as the first factor and estrogen treatment as the second (control or estradiol). Heifers were ovariectomized at ∼4.5 mo of age, and estrogen treatments were initiated 1 mo later. After 3 days of treatment, gene expression was analyzed in the parenchyma and fat pad of the bovine mammary gland using a high-density oligonucleotide microarray. Oligonucelotide probes represented 40,808 tentative consensus sequences from TIGR Bos taurus Gene Index and 4,575 singleton expressed sequence tags derived from libraries of pooled mammary gland and gut tissues. Microarray data were analyzed by use of the SAS mixed procedure, with an experiment-wide permutation-based significance level of P < 0.1. Considerable differences in basal gene expression were noted between mammary parenchyma and fat pad. A total of 124 estrogen-responsive genes were identified, with most responding only in the parenchyma or the fat pad. The majority of genes identified were not previously reported to be estrogen responsive. These undoubtedly include genes that are regulated indirectly but also include known estrogen-targeted genes and novel genes with potential estrogen-responsive elements in their promoter regions. The distinctive expression patterns regulated by estrogen in parenchyma and fat pad shed light on the need for both tissues to obtain normal mammary development.

OXYGEN UPTAKE OF RAT MAMMARY TISSUE SLICES

1950 ◽  
Vol 28e (5) ◽  
pp. 217-221 ◽  
Author(s):  
Jules Tuba ◽  
Herbert E. Rawlinson ◽  
Lorna Glen Shaw
Keyword(s):  
Mammary Gland ◽  
Oxygen Uptake ◽  
In Vitro Study ◽  
Female Rats ◽  
Male Rats ◽  
Mammary Tissue ◽  
Oxygen Utilization ◽  
Tissue Slices ◽  
Mammary Gland Tissue

An in vitro study has been made of the oxygen uptake of mammary gland tissue of female rats in various experimental states. Because of the very high proportion of fat in mammary tissue the values of [Formula: see text] are determined on a fat-free as well as a water-free basis, thus providing a more accurate measure of the oxygen consumption of this tissue. The oxygen utilization by mammary gland of pregnant animals is increased approximately three times over the activity in the normal, or resting, gland. This increase is maintained during lactation and a return toward normal levels occurs during postlactational involution. The response to p-phenylenediamine indicated that during lactation the increased energy requirements decreased the reserves of the cytochrome system in mammary tissue. There is a well developed mammary gland in adult male rats; but the average fat content and response to p-phenylenediamine of the tissue are almost identical with values for adult female rats. The use of p-phenylenediamine as a histological stain for the cytochrome system in mammary tissue is described.

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