Response Of Mammary Gland Research Articles

Reproductive tissue selective actions of progesterone receptors.

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 activities in vitro. To delineate the individual roles of PR-A and PR-B in 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.

No Association between the Progesterone Receptor Gene +331G/A Polymorphism and Breast Cancer

No Association between the Progesterone Receptor Gene <i>+331G/A</i> Polymorphism and Breast Cancer

Increased Levels of LPS-Binding Protein in Bovine Blood and Milk Following Bacterial Lipopolysaccharide Challenge

Several species of gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, and various species of Enterobacter, are common mastitis pathogens. All of these bacteria are characterized by the presence of endotoxin or lipopolysaccharide (LPS) in their outer membrane. The bovine mammary gland is highly sensitive to LPS, and LPS has been implicated, in part, in the pathogenesis of gram-negative mastitis. Recognition of LPS is a key event in the innate immune response to gram-negative infection and is mediated by the accessory molecules CD14 and LPS-binding protein (LBP). The objective of the current study was to determine whether LBP levels increased in the blood and mammary gland following LPS challenge. The left and right quarters of five midlactating Holstein cows were challenged with either saline or LPS (100μg), respectively, and milk and blood samples collected. Basal levels of plasma and milk LBP were 38 and 6μg/ml, respectively. Plasma LBP levels increased as early as 8h post-LPS challenge and reached maximal levels of 138μg/ml by 24h. Analysis of whey samples derived from LPS-treated quarters revealed an increase in milk LBP by 12h. Similar to plasma, maximal levels of milk LBP (34μg/ml) were detected 24h following the initial LPS challenge. Increments in milk LBP levels paralleled a rise in soluble CD14 (sCD14) levels and initial rises in the levels of these proteins were temporally coincident with maximal neutrophil recruitment to the inflamed gland. Because LBP and sCD14 are known to enhance LPS-induced host cell activation and to facilitate detoxification of LPS, these data are consistent with a role for these molecules in mediating mammary gland responses to LPS.

Neonatal infection with a milk-borne virus is independent of β7 integrin- and L-selectin-expressing lymphocytes

Mouse mammary tumor virus (MMTV) is acquired by neonates through milk and first infects lymphocytes in Peyer's patches. We show here that newborn mice lacking beta7 integrin or L-selectin were infected with MMTV at wild-type levels in both their lymphoid and mammary tissues. Superantigen-mediated activation and cognate T cell deletion were also unimpaired in both types of null mice. A large proportion of neonatal Peyer's patch lymphocytes in wild-type mice were beta7 and beta1 integrin low and both populations increased in response to MMTV infection. These results suggest that adhesion molecules other than beta7 integrin or L-selectin play a role in lymphocyte homing in the gut, peripheral lymph nodes and mammary gland in response to MMTV infection.

The Mouse Uterotrophic Assay: Other End Points

CorrespondenceOpen AccessThe Mouse Uterotrophic Assay: Other End Points RR Newbold RR Newbold Search for more papers by this author Published:1 December 2001https://doi.org/10.1289/ehp.109-a569aCited by:8AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit FiguresReferencesRelatedDetailsCited by Jung E, An B, Choi K and Jeung E (2012) Potential estrogenic activity of triclosan in the uterus of immature rats and rat pituitary GH3 cells, Toxicology Letters, 10.1016/j.toxlet.2011.10.017, 208:2, (142-148), Online publication date: 1-Jan-2012. Dixon D, Reed C, Moore A, Gibbs-Flournoy E, Hines E, Wallace E, Stanko J, Lu Y, Jefferson W, Newbold R and Fenton S (2012) Histopathologic changes in the uterus, cervix and vagina of immature CD-1 mice exposed to low doses of perfluorooctanoic acid (PFOA) in a uterotrophic assay, Reproductive Toxicology, 10.1016/j.reprotox.2011.10.011, 33:4, (506-512), Online publication date: 1-Jul-2012. Vo T and Jeung E (2009) An Evaluation of Estrogenic Activity of Parabens Using Uterine Calbindin-D9k Gene in an Immature Rat Model, Toxicological Sciences, 10.1093/toxsci/kfp176, 112:1, (68-77), Online publication date: 1-Nov-2009., Online publication date: 1-Nov-2009. Di X, Yu L, Moore A, Castro L, Zheng X, Hermon T and Dixon D (2008) A low concentration of genistein induces estrogen receptor-alpha and insulin-like growth factor-I receptor interactions and proliferation in uterine leiomyoma cells, Human Reproduction, 10.1093/humrep/den087, 23:8, (1873-1883), Online publication date: 1-Aug-2008., Online publication date: 1-Aug-2008. Groothuis P, Dassen H, Romano A and Punyadeera C (2007) Estrogen and the endometrium: lessons learned from gene expression profiling in rodents and human, Human Reproduction Update, 10.1093/humupd/dmm009, 13:4, (405-417), Online publication date: 1-Jul-2007. Vandenberg L, Wadia P, Schaeberle C, Rubin B, Sonnenschein C and Soto A (2006) The mammary gland response to estradiol: Monotonic at the cellular level, non-monotonic at the tissue-level of organization?, The Journal of Steroid Biochemistry and Molecular Biology, 10.1016/j.jsbmb.2006.06.028, 101:4-5, (263-274), Online publication date: 1-Nov-2006. Newbold R, Jefferson W, Padilla-Banks E and Haseman J (2004) Developmental exposure to diethylstilbestrol (DES) alters uterine response to estrogens in prepubescent mice: low versus high dose effects, Reproductive Toxicology, 10.1016/j.reprotox.2004.01.007, 18:3, (399-406), Online publication date: 1-May-2004. Lomnitski L, Padilla-Banks E, Jefferson W, Nyska A, Grossman S and Newbold R (2003) A Natural Antioxidant Mixture from Spinach Does Not Have Estrogenic or Antiestrogenic Activity in Immature CD-1 Mice, The Journal of Nutrition, 10.1093/jn/133.11.3584, 133:11, (3584-3587), Online publication date: 1-Nov-2003. Vol. 109, No. 12 December 2001Metrics About Article Metrics Publication History Originally published1 December 2001Published in print1 December 2001 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Starvation Increases the Amount of Pyruvate Dehydrogenase Kinase in Several Mammalian Tissues

Covalent modification of the pyruvate dehydrogenase complex provides an important regulatory mechanism for controlling the disposal of glucose and other compounds metabolized to pyruvate. Regulation of the complex by this mechanism is achieved in part by tissue-specific expression of the genes encoding isoenzymes of pyruvate dehydrogenase kinase (PDK). Starvation is known from our previous work to increase PDK activity of heart and skeletal muscle by increasing the amount of PDK isoenzyme 4 (PDK4) present in these tissues. This study demonstrates that increased expression of both PDK4 and PDK2 occurs in rat liver, kidney, and lactating mammary gland in response to starvation. PDK4 and PDK2 message levels were also increased by starvation in the two tissues examined (liver and kidney), suggesting enhancement of gene transcription. Changes in PDK2 message and protein were of similar magnitude, but changes in PDK4 message were greater than those in PDK4 protein, suggesting regulation at the level of translation. In contrast to these tissues, starvation had little or no effect on PDK2 and PDK4 protein in brain, white adipose tissue, and brown adipose tissue. Nevertheless, PDK4 message levels were significantly increased in brain and white adipose tissue by starvation. The findings of this study indicate that increased expression of PDK isoenzymes is an important mechanism for bringing about inactivation of the pyruvate dehydrogenase complex during starvation in many but not all tissues of the body. The absence of this mechanism preserves the capacity of neuronal tissue to utilize glucose for energy during starvation.

HOXA5 Regulates Expression of the Progesterone Receptor

The majority of breast carcinomas show reduced or no expression of the transcription factor, HOXA5. Recently, we have shown that HOXA5 is a potent transactivator of p53 in breast cells and thus may affect the response of breast cancer cells to DNA damage. To determine whether HOXA5 played a role in growth and homeostasis in breast cells, we studied its interaction with the progesterone receptor. The progesterone receptor (PR) belongs to the superfamily of nuclear receptors whose members co-ordinate morphogenesis of the mammary gland in response to binding to their cognate ligands. An increased expression of the endogenous PR gene was seen in MCF-7 cells following induced expression of an exogenously transfected HOXA5 gene. HOXA5, but not HOXB4, -B5, or -B7 activated the PR promoter in two breast cancer cell lines, MCF-7 and Hs578T. Deletion and mutation analysis of the promoter identified a single HOXA5-binding site required for transactivation of the PR gene by HOXA5. HOXA5 binds directly to this site in the PR promoter. Thus, HOXA5 may behave as a transcriptional regulator of multiple target genes, two among which are p53 and the progesterone receptor.

Mammary infection with Staphylococcus aureus in cows: progress from inoculation to chronic infection and its detection.

The progress of Staphylococcus aureus infection from inoculation to the early chronic stage was examined in 12 Israeli-Holstein cows (four primiparous and eight multiparous) for up to 48 d after inoculation. Before inoculation, the primiparous cows were free from any infection and the multiparous cows were infected by coagulase-negative staphylococci. Two quarters in each cow were inoculated intracisternally following milking with 2000 cfu of a local prevailing Staph. aureus strain, VL-8407. Infection was established in 21 out of 24 quarters. The control quarters remained free from infection during the study, with no significant change in function. No statistically significant differences were found between primiparous and multiparous cows in the responses examined. Somatic cell count (SCC) increased within 24 h of inoculation and remained high for the duration of the study. In the infected quarters mean ln (SCC) increased within 24 h from 9.9 +/- 0.5 before inoculation to 13.0 +/- 0.2 after inoculation; most of the cells were neutrophils. N-acetyl-beta-glucosaminidase activity, expressed as ln (nnmol/min per l), was increased from 0.9 +/- 0.6 to 2.4 +/- 0.2 by inoculation, and was highly correlated with SCC. The Staph. aureus count fluctuated with no particular relationship with SCC. The phagocytic activity of neutrophils was significantly lower in the inoculated than in the control quarters and this difference increased with time after inoculation. CD8+ T lymphocytes were the main subpopulation of lymphocytes found in inoculated quarters. After inoculation, maximum but not minimum electrical conductivity (EC) recorded during milking increased significantly. The rises in maximum EC varied significantly among cows. The rises in SCC were associated with a persistent increase in EC in only one of the eight cows examined. No clinical signs were observed, and milk yield and composition were not affected during the study period. The results suggest that some strains of Staph. aureus may induce a relatively mild response in mammary glands of cows in mid lactation, and that the concomitant development of such chronic Staph. aureus infections in two quarters may not be detected by changes in the EC of composite milk and in the yield of the cow.

Amino Acid Exchange by the Mammary Gland of Lactating Goats when Histidine Limits Milk Production

The aim of this study was to monitor amino acid (AA) exchange kinetics of the mammary gland in response to an imposed limitation on His supply for milk production. Lactating goats (n = 4, ~120 DIM) were fed a low protein ration that provided only 77% of metabolizable protein and 100% of energy requirements for milk production. The protein deficiency was alleviated by infusion into the abomasum of an AA mixture (67 g/d) including (+H; 4.4 g/d) or excluding (-H) His. Goats were assigned to treatments (6 to 7 d) according to a switchback design. On the last day of the first two periods, [U-13 C]AA were continuously infused i.v. for 7h and arterial and mammary vein blood was withdrawn to determine plasma AA concentration and enrichment. Flow probes monitored mammary blood flow. The secretion and enrichments of AA in milk casein were monitored each hour. A three-pool model of the gland was used to derive bi-directional rates of plasma AA exchange. Arterial plasma His concentration was lower during -H infusion (8 vs. 73 µM), but those of other AA changed little. Responses to low levels of plasma His were: 1) mammary blood flow increased by ~33%; 2) the gland's capacity to remove plasma His increased 43-fold, whereas the gland's capacity for other AA declined by two- to threefold; and 3) influx and efflux of His by the gland decreased. Thus, as the reduction in His efflux was insufficient to offset the reduced influx, milk protein yield decreased from 118 to 97 g/d.

Chemical carcinogen-induced tumorigenesis in parous, involuted mouse mammary glands.

Chemical carcinogen-induced tumorigenesis in parous, involuted mouse mammary glands.

Evaluation of the role of endotoxin and cortisol on modulation of CD18 adhesion receptors in cows with mastitis caused by Escherichia coli

Abstract Objective To determine the effect of mastitis caused by Escherichia coli on expression of CD18 cell surface receptors and to evaluate the involvement and regulation of receptors by lipopolysaccharide (LPS) and cortisol. Animals 11 clinically normal lactating Holstein-Friesian cows. Procedure Binding of CD18 monoclonal antibodies to neutrophils was studied, using flow cytometry, before and after intramammary inoculation of E coli organisms. Effect of LPS and cortisol on expression of adhesion receptors was investigated, using a whole-blood model. Results Expression of CD18 adhesion receptors on bovine neutrophils increased 35% by 12 hours after intramammary inoculation of E coli. By 24 hours after inoculation, the number of receptors had returned to control values. High cortisol concentrations (100 nmol/L) were seen 12 to 18 hours after inoculation. Addition of LPS to blood induced a 30% increase in the number of CD18 receptors, and maximal number of receptors was expressed at an LPS concentration of 0.1 ng/ml. A decrease in the number of CD18 receptors was induced by incubation with cortisol or dexamethasone before challenge-exposure with LPS. Conclusions An increase in the number of CD18 receptors on neutrophils is mediated by local production of LPS. Subsequent endogenous release of cortisol may prevent additional increases in the number of receptors. Clinical Relevance During acute mastitis caused by E coli, there is an increase in the number of CD18 receptors on circulating neutrophils. Cortisol induces a decrease in the number of CD18 receptors, probably modulating the acute inflammatory response in mammary glands of lactating cows. (Am J Vet Res 1999;60:534–540)

Paralogous mouse Hox genes, Hoxa9, Hoxb9, and Hoxd9, function together to control development of the mammary gland in response to pregnancy.

Although the role of Hox genes in patterning the mammalian body plan has been studied extensively during embryonic and fetal development, relatively little is known concerning Hox gene function in adult animals. Analysis of mice with mutant Hoxa9, Hoxb9, and Hoxd9 genes shows that these paralogous genes are required for mediating the expansion and/or differentiation of the mammary epithelium ductal system in response to pregnancy. Mothers with these three mutant genes cannot raise their own pups, but the pups can be rescued by fostering by wild-type mothers. Histologically, the mammary glands of the mutant mothers seem normal before pregnancy but do not develop properly in response to pregnancy and parturition. Hoxa9, Hoxb9, and Hoxd9 are expressed normally in adult mammary glands, suggesting a direct role for these genes in the development of mammary tissue after pregnancy. Because loss-of-function mutations in these Hox genes cause hypoplasia of the mammary gland after pregnancy, it may be productive to look for misexpression of these genes in mammary carcinomas.

Role of epidermal growth factor in the acquisition of ovarian steroid hormone responsiveness in the normal mouse mammary gland.

The purpose of the present studies was to investigate the role of epidermal growth factor (EGF) in the acquisition of estrogen (E) and progestin (P) responsiveness in the mouse mammary gland in vivo. Using the Elvax 40P implant technique to introduce bioactive molecules directly into the mammary gland to produce a localized effect, we have made the novel observation that EGF implanted into glands of pubertal mice followed by E treatment resulted in the precocious acquisition of E-inducible progesterone receptors (PR). In sexually mature mice, EGF implants alone were able to increase PR. A neutralizing antibody specific for EGF blocked E-dependent stimulation of end-bud development and PR induction. Furthermore, the antiestrogen ICI 182,780 blocked the EGF-induced stimulation end-buds and PR induction, indicating that these EGF effects are mediated via estrogen receptors (ER). Immunohistochemical analysis showed that the endogenous EGF content of mammary glands of mature mice was higher than pubertal mice, that E implants caused a localized increase in mammary gland EGF content in both pubertal and mature mice, and that in mature mice E caused an increase in stromal cell EGF content. We have previously shown that the acquisition of E-inducible PR can be modulated by mammary stroma, and the present results indicate that mammary stroma could modulate hormonal responsiveness through control of local growth factor concentration. Taken together, these results provide evidence that E-dependent responses of mouse mammary gland in vivo, such as end-bud proliferation and PR regulation, may be mediated by EGF through an ER-dependent mechanism.

The role of pyruvate dehydrogenase, phosphofructo-1-kinase and acetyl-CoA carboxylase in the regulation of fatty acid synthesis in the lactating rat mammary gland during the starved to re-fed transition

Re-feeding 24-h-starved lactating rats resulted in a rapid (within 0.5 h) restoration of glucose uptake by the mammary gland and a slower (within 3 h) restoration of fatty acid synthesis. The rapid reactivation of glucose uptake (82% of fed value within 0.5 h of re-feeding) correlated with a rapid reactivation of 6-phosphofructo-1-kinase (6-PF-1-K) and glycolysis (as determined by a 97% decrease in the [fructose-6-phosphate]/[fructose-1,6-bisphosphate] ratio). This could not be fully explained by a fall (29%) in the tissue concentration of its allosteric inhibitor, citrate. The delayed reactivation of pyruvate dehydrogenase (PDH) correlated very closely with the delayed reactivation of fatty acid synthesis and explained the continued output of pyruvate and lactate within the first 0.5 h of re-feeding. PDH reactivation preceded the reactivation of acetyl-CoA carboxylase (ACC), which did not occur significantly until 1.5 h of re-feeding. ACC reactivation correlated with a decrease in the tissue concentration of citrate and a second late phase of 6-PF-1-K activation. It is clear that the important regulatory steps 6-PF-1-K, PDH and ACC, are reactivated asynchronously in the lactating mammary gland in response to re-feeding starved rats and that PDH is more important than ACC in the regulation of fatty acid synthesis.

The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues.

We have examined the developmental expression of the murine breast and ovarian cancer susceptibility gene, Brca1, to investigate its role in the control of cell growth and differentiation. Specifically, we have analysed Brca1 expression during embryonic development, in adult tissues, and during postnatal mammary gland development, particularly in response to ovarian hormones. Our results suggest that Brca1 is expressed in rapidly proliferating cell types undergoing differentiation. In the mammary gland, Brca1 expression is induced during puberty, pregnancy, and following treatment of ovariectomized animals with 17 beta-estradiol and progesterone. These observations imply that Brca1 is involved in the processes of proliferation and differentiation in multiple tissues, notably in the mammary gland in response to ovarian hormones.

Control of Mammary Epithelial Cell DNA Synthesis by Epidermal Growth Factor, Cholera Toxin, and IGF-1: Specific Inhibitory Effect of Prolactin on EGF-Stimulated Cell Growth

Epidermal growth factor (EGF) stimulates mouse mammary cell proliferation in vivo , but its maximal level in the mammary gland is at midlactation, when little mammary growth takes place. The present studies use a normal murine mammary gland epithelial cell line (NMuMG) to determine the effects of the mammary mitogens EGF, cholera toxin (CT), and insulin-like growth factor-1 (IGF-1) on cell proliferation and how cell growth is altered by addition of the lactogenic hormone prolactin (PRL). EGF and CT stimulated over a fourfold increase of DNA synthesis in NMuMG cells when compared to basal levels. Only a twofold stimulation of DNA synthesis was observed when cells were treated with IGF-1. There was a slight increase in the percentage of cells in S-phase when these agents were added in combination with each other. Physiological levels of PRL had no significant effect on CT- or IGF-1-induced DNA synthesis but reduced EGF-stimulated cell proliferation to basal levels. Furthermore, PRL reduced the percentage of cells in S-phase to IGF-1- and CT-induced levels in the presence of EGF. Interestingly, PRL increased cellular levels of EGF mRNA after 2 h of treatment, which is similar to the response of mouse mammary glands cultured in lactogenic hormones. We conclude that even though PRL can increase the amount of EGF mRNA in mammary epithelial cells, it also eliminates EGF-induced mitogenesis.

Transferrin gene expression in the mammary gland of the rat. The enhancing effect of 17 beta-oestradiol on the level of RNA is tissue-specific.

We have investigated the physiological factors which regulate transferrin gene expression in the mammary gland of the rat. Our studies by dot blot analysis have demonstrated that multiple doses of 17 beta-oestradiol (OE2; 0.5 mg/kg per day for 3 days) elicit a specific 3.5-fold increase in the transferrin mRNA levels in the mammary glands of virgin rats. The hormonal action of OE2 in mammary tissue was specific for the transferrin gene, as judged by hybridization with beta-actin cDNA. The accumulation of transferrin mRNA induced by OE2 treatment was similar to the developmentally regulated expression of the gene observed during the reproductive cycle. The steady-state level of mammary transferrin mRNA increased by up to 4.5-fold at day 21 of lactation, when compared with virgin and pregnant rats. Our results show that the pattern of transferrin gene expression is different in mouse and rat mammary glands. The specific response of the transferrin gene to OE2 was not found in the liver or in the uterus. In the uterus alone, OE2 produced a significant increase in the content of nucleic acids and also induced the accumulation of transferrin and beta-actin mRNAs. We have detected for the first time an induction of transferrin gene expression in the mammary gland in response to OE2, and these results support the view that the pattern of transferrin gene multi-modulated expression is tissue- and species-specific.

Histologic Response of the Heifer Mammary Gland to Intramammary Infusion of Interleukin-2 or Interferon-γ

The histologic and cytologic responses of heifer mammary glands infected with Staphylococcus aureus were studied after infusion of interleukin-2 or interferon-γ. Two groups of 4 heifers each, which were infected experimentally with S. aureus in all 4 mammary quarters, were infused in diagonal quarters with 7.5×105 units of interleukin-2 or 105 units of interferon-γ; remaining quarters received PBS. Heifers in both trials were slaughtered 14 d after cytokine infusion, and mammary tissues were collected for histological examination. Uninfected quarters from 2 additional heifers were left untreated to compare infected with uninfected tissues for both trials. Morphologic evaluation and leukocyte infiltration scores were performed on tissue sections stained with hematoxylin and eosin, and plasma cells were quantified on sections stained with immunoperoxidase. Infected quarters had lower percentages of alveolar epithelial and luminal areas and higher percentages of stromal area than did uninfected quarters in the interleukin-2 trial, but no differences were observed between infected quarters that had been treated with PBS or interleukin-2. Likewise, interferon-γ treatment had no effect on mammary parenchymal components in the infected quarters. Interleukin-2 treatment significantly elevated leukocytosis into the mammary gland parenchyma compared with infected quarters treated with PBS and uninfected quarters. Among the leukocyte types evaluated. eosinophilic infiltration was elevated in interleukin-2 quarters over that of PBS controls. In both trials, concentrations of plasma cells bearing Ig were elevated in infected versus uninfected quarters. Plasma cell concentrations also were higher in cytokine than PBS controls, especially in interleukin-2 quarters. Results suggested that neither cytokine influenced the histology of infected mammary tissues, but both interleukin-2 and interferon-γ increased, although insignificantly, the prevalence of all isotypes of plasma cells bearing Ig, suggesting enhancement of the local immune response to IMI.

Radiotelemetry temperature responses of mammary gland and body to intramammary injection of Escherichia coli endotoxin or Streptococcus agalactiae in lactating dairy cows

Summary To investigate the feasibility of using changes in body or mammary temperature to detect mastitis, radiotransmitters were implanted midway between rear udder quarters and in the peritoneal cavity of 5 Holstein cows (1 to 3 months in lactation) housed in an environmental chamber (16 ± 2 C; lights on 7:00 am to 11:00 pm). After a 6-week control period, Escherichia coli endotoxin (0.5 mg) was injected after the morning milking into left rear teat cisterns via the teat canal. Wisconsin mastitis test score and somatic cell count in all quarters increased significantly (P &lt; 0.01) by the next milking. Effects were greatest in the endotoxin-exposed quarters. Milk yields for all quarters decreased significantly (P &lt; 0.01) by the first milking after endotoxin injection. Udder and body temperatures at milkings were similar and were not affected by treatment. When temperatures were averaged for the 5 cows for each of 120 time points/d, average temperatures, relative to time of injection of endotoxin, were increased by 0.5 C above baseline at 2.75 hours, peaked at +2.9 C at 6.50 hours, and remained high through 9.25 hours after injection. Power spectra calculated for individual cows on a daily basis universally indicated an increase in power at low frequencies on the day of injection. Subsequently, Streptococcus agalactiae (200 colony-forming units) was injected into right rear teat cisterns. Wisconsin mastitis test score increased at the second milking after injection. Cell count and quarter milk yield decreased by the third milking. As with endotoxin, injection of S agalactiae could not be detected via a change in temperature at milkings. Of the 5 cows, 3 had a peak in temperature after injection of S agalactiae. Average temperatures for these 3 cows relative to time of injection, were increased by 0.5 C above baseline at 24.25 hours, peaked at + 1.4 C at 26.25 hours, and remained high through 28.75 hours after injection. Power spectra calculated for the day in which a temperature peak was detected for these 3 cows indicated an increase in power at low frequencies, compared with spectra for all other days. Similar increases in power were also detected for the 2 cows that did not have temperature peaks. When clinical signs of mastitis are obvious at milking, there is little advantage of using body temperature for detection of infection. When clinical signs are not obvious, body temperature is often only minimally increased. Thus, monitoring body temperature at milkings adds little to the ability to detect mastitis. Of more interest is the ability to detect transient temperature increases that often develop in association with less-severe infections. Also, as early treatment increases the likelihood of successful treatment, detection of the onset of temperature increases would be advantageous for treatment of severe infections. Detection of a transient temperature peak requires taking temperature readings every 2 hours. To detect mastitis when a temperature peak does not occur requires measurement every 15 minutes to calculate power spectra. The ability to detect the onset of acute clinical infections and subclinical infections, using frequent temperature readings, indicates that development of a practical radiotelemetry system for use on farms may be warranted, depending on cost. The added potential of using body temperature to monitor general health and to detect estrus enhances the economic feasibility of developing such a system.

Mammary gland morphology and responsiveness to regulatory molecules following prenatal exposure to diethylstilbestrol.

Female ACI rats were exposed to diethylstilbestrol (DES) in utero to evaluate the effects on the peri-pubertal mammary gland with respect to 1) mammary gland morphology, 2) sensitivity to natural and synthetic estrogens, and 3) sensitivity to endogenous epidermal growth factor (EGF). Pregnant rats were injected with vehicle (sesame oil) or DES (total dose, 8.0 micrograms) on days 15 and 18 of gestation. DES-exposed and control offspring were ovariectomized at 34 days of age and sacrificed at day 53 to ascertain the morphology of the mammary glands in peri-pubertal rats. Elvax pellets containing 5 or 11 ng 17 beta-estradiol (E2) or DES were implanted subcutaneously adjacent to the third mammary gland pair. Furthermore, additional groups of rats were subjected to bilateral sialoadenectomy at the day of ovariectomy to remove the major source of endogenous EGF. A significant proportion of mammary glands of DES-exposed animals exhibited atypical mammary gland morphology, with approximately 25% displaying hypo-differentiation, and about 5% with aberrant hyper-proliferation. From the pellet implantation experiments, the DES-exposed glands were found to be refractory to stimulation by 5 and 11 ng DES; however, there was no significant difference in the degree of local stimulation elicited by either dose of E2. Sialoadenectomy at d34 had no apparent effect on mammary gland morphology in either the DES-exposed or vehicle-exposed groups. These data support the premise that the mammary gland of the peri-pubertal ACI rat is morphologically and physiologically aberrant as a function of transplacental exposure to DES, with a significant percentage hypo-differentiated and refractory to subsequent hormonal stimulation.