RESUMO
Regulation of interleukin-1 (IL-1) mediated biological responses is complicated by the multiple ligands and receptors of the IL-1 family. Most studies of IL-1 receptors have used human or rodent cells. Here, we report that the coding region of the bovine type 1 interleukin-1 receptor (type 1 IL-1R) cDNA extends 1719 bp in length. Northern analysis of specific bovine cell and tissue RNA demonstrated a 4.5 kb transcript. Overall, the bovine type 1 IL-1R coding region exhibits approximately 81 and 76% similarity with the human type 1 IL-1R at the nucleotide and amino acid level, respectively, and somewhat less similarity with the mouse and rat sequences. Type 1 IL-1R transcripts were confirmed by RT-PCR in several bovine cell types, including peripheral blood mononuclear cells (PBMCs), neutrophils (PMNs), and fibroblast, peritoneal macrophage, and arterial endothelial cell lines. It is expected that molecular clones for the bovine type 1 and 2 IL-1 receptors will provide us with the tools needed to decipher species-and cell-specific regulation of IL-1 action in the bovine.
Assuntos
Bovinos/imunologia , DNA Complementar/química , Receptores de Interleucina-1/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Clonagem Molecular , Humanos , Camundongos , Dados de Sequência Molecular , Ratos , Receptores de Interleucina-1/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Especificidade da EspécieRESUMO
Interleukin-1 is a key player in inflammation and the immune response. The interleukin-1 family consists of three ligands (IL-1 alpha, IL-1 beta, and the IL-1 receptor antagonist) and two receptors (IL-1RI and IL-1RII). Previous studies suggest a dynamic relationship among these receptors and ligands that regulates the magnitude and extent of IL-1 mediated activities. Our laboratory has cloned and sequenced the bovine type I and II interleukin-1 receptors, and has begun to investigate their regulation in bovine leukocytes in vitro and in vivo. IL-1RI and IL-1RII mRNA levels were upregulated in vitro by various mediators, including dexamethasone, rBoIL-4, rBoGM-CSF, and rHuTNF alpha. Conversely, IL-1RI mRNA levels were down-regulated by IFN-gamma. An in vivo study indicated that IL-1RII mRNA levels increased earlier than IL-1RI mRNA levels in dexamethasone-treated cattle. These findings suggest that early upregulation of IL-1RII, which is a decoy receptor, may be part of the anti-inflammatory action of glucocorticoids. Our investigations suggest that anti-inflammatory agents increase expression of the biologically inactive IL-1RII, as compared with the biologically active IL-1RI, in bovine leukocytes.
Assuntos
Bovinos/imunologia , Receptores de Interleucina-1/metabolismo , Animais , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas In Vitro , Mediadores da Inflamação/imunologia , Interleucina-1/imunologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina-1/genética , Receptores Tipo I de Interleucina-1 , Receptores Tipo II de Interleucina-1RESUMO
The effects of active immunization against inhibin on production performance in female Japanese quail (Coturnix coturnix japonica) were assessed in two separate trials using an MBP-cINA521 fusion protein as an immunogen. The fusion protein, MBP-cINA521, consisted of the bacterial maltose binding protein (MBP) and a truncated form of the mature alpha-subunit of chicken inhibin (cINA521). MBP-cINA1521 was constructed by: 1) excising a 521-bp PstI fragment from a chicken inhibin alpha-subunit cDNA (cINA6; gift of P. A. Johnson), 2) cloning this fragment, which encodes all but the first 11 amino acid residues of the mature alpha-subunit, into the pMal-c2 vector of the MBP fusion expression system, and 3) expressing the fusion protein (MBP-cINA521) from the Escherichia coli and purifying it using affinity chromatography. In each trial, quail were randomly and equally assigned to one of two injection treatments as follows: 1) MBP-cINA521 in Freund's adjuvant, or 2) Freund's adjuvant (vehicular controls; CON). All immunizations were given subcutaneously and Freund's complete and incomplete adjuvant were used for primary and booster injections, respectively. In Trial 1, birds were given a primary challenge of 0.2 mg MBP-cINA521 per bird at 25 d of age, followed by booster immunizations (0.1 mg MBP-cINA521 per bird) at 33, 40, 47, 54 and 61 d of age and every 35 d thereafter. The CON birds received vehicular immunizations at the same time intervals. In Trial 2, birds treated with MBP-cINA521 received a primary challenge of 0.2 mg MBP-cINA521 per bird at 26 d of age, followed by booster immunizations (0.1 mg MBP-cINA521 per bird) using the same schedule as that used in Trial 1, with the exception that no boosters were given after 61 d of age. The CON birds received vehicular immunizations at the same time intervals. Collection of production performance data was initiated coincident with the laying of the first egg in each trial (i.e., beginning at 41 and 44 d of age for Trials 1 and 2, respectively) and continued for 30 1-wk periods of lay. Combined data from Trials 1 and 2 indicated that the mean +/- SE age at first egg lay was markedly decreased (P < 0.005) in MBP-cINA521-treated quail (53.4 +/- 0.9 d of age) when compared to the CON (57.6 +/- 1.3 d of age). Likewise, the mean +/- SE age at 50% egg production was reduced (P < 0.03) in quail immunized against inhibin (65.4 +/- 2.1 d of age) when compared to the CON (77.6 +/- 4.7 d of age). Total hen-day egg production was also higher (P < 0.05, Trial 1; P < 0.01, Trial 2) in MBP-cINA521-treated quail (88.7 +/- 1.4%, Trial 1; 90.1 +/- 1.2%, Trial 2) than in the CON birds (81.9 +/- 2.9%, Trial 1; 73.6 +/- 6.5%, Trial 2). Collectively, these findings provide evidence that inhibin immunoneutralization accelerated puberty and enhanced hen-day egg production during a 30-wk period of egg lay in Japanese quail.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Coturnix/fisiologia , Ovos/normas , Proteínas de Escherichia coli , Inibinas/imunologia , Proteínas de Transporte de Monossacarídeos , Oviposição , Vacinação/veterinária , Vacinas Sintéticas , Animais , Proteínas de Transporte/biossíntese , Proteínas de Transporte/imunologia , Clonagem Molecular , Escherichia coli , Feminino , Inibinas/biossíntese , Proteínas Ligantes de Maltose , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/imunologiaRESUMO
A 39 kilodalton glycoprotein has been isolated from bovine mammary secretions by heparin-agarose affinity chromatography and gel filtration. It is a minor whey protein in mammary secretions collected during the nonlactating period, but is clearly detectable by affinity chromatographic and immunoblotting techniques. It is not detectable by these techniques in milk or colostrum. This protein is not immunologically related to milk proteins, serum proteins or cytoskeletal proteins. The N-terminal amino acid sequence (36 amino acids) is not similar to other known proteins. Isolating this novel 39 kilodalton protein provides a specific marker for mammary function during the nonlactating period.
Assuntos
Glândulas Mamárias Animais/metabolismo , Proteínas do Leite/isolamento & purificação , Acetilglucosaminidase/metabolismo , Animais , Bovinos , Cromatografia de Afinidade , Cromatografia em Gel , Colostro/análise , Eletroforese em Gel de Poliacrilamida , Feminino , Glicoproteínas/isolamento & purificação , Imunodifusão , Técnicas Imunoenzimáticas , Manosil-Glicoproteína Endo-beta-N-Acetilglucosaminidase , Leite/análise , Peso Molecular , Proteínas do Soro do LeiteRESUMO
Proteins in mammary secretions were examined during the dry period of four cows. Polyacrylamide gel electrophoresis was used to determine relative changes in the electrophoretic profiles of whey proteins in the mammary secretions. Concentrations of beta-lactoglobulin and alpha-lactalbumin in dry cow secretions were determined by immunoassay. Concentrations of both proteins changed in parallel during the dry period. Concentrations of beta-lactoglobulin and alpha-lactalbumin decreased during the first 30 d of the dry period but generally remained above .1 mg/ml secretion. A transient increase in beta-lactoglobulin and alpha-lactalbumin concentrations occurred at about 40 d after drying-off, prior to the prepartum increase.
Assuntos
Lactalbumina/análise , Lactação , Lactoglobulinas/análise , Glândulas Mamárias Animais/metabolismo , Animais , Bovinos , Eletroforese em Gel de Poliacrilamida , Feminino , Proteínas do Leite/análise , Gravidez , Proteínas do Soro do LeiteRESUMO
Bovine lactoferrin in involuting mammary tissue was identified by immunohistochemistry and tissue explant culture. Immunoreactive lactoferrin was associated with mammary epithelial cells. Immunostaining for lactoferrin increased during involution, in contrast to declining immunostaining of epithelia for the milk-specific protein beta-lactoglobulin. Immunostaining for lactoferrin also was observed at the basal region of alveolar epithelia, perhaps in association with basement membrane components. Lactoferrin was preferentially synthesized in involuting mammary tissue compared with lactating tissue. Synthesis of lactoferrin in the involuting mammary gland occurs despite the apparent decline in synthesis of milk-specific proteins.
Assuntos
Lactoferrina/análise , Glândulas Mamárias Animais/química , Animais , Bovinos , Epitélio/química , Feminino , Imuno-Histoquímica , Lactoferrina/biossíntese , Lactoglobulinas/análise , DesmameRESUMO
Enzyme-linked immunosorbent assays were developed for two proteins found in mammary secretions during the non-lactating period: lactoferrin and a 39-kdal protein. Minimum detectable concentrations were .12 ng/ml for lactoferrin and .0037 ng/ml for the 39-kdal protein. Standard curves were linear in the ranges of .4 to 100 ng/ml for lactoferrin and 2.4 to 30 ng/ml for the 39-kdal protein. The immunoassays were used to measure concentrations of the proteins in mammary secretions during involution. From the last day of milking to d 30 of involution, mean concentrations of lactoferrin and the 39-kdal protein increased from .82 +/- .35 to 78.5 +/- 12.43 mg/ml and from 11.8 +/- 3.8 to 84.4 +/- 21.1 micrograms/ml, respectively. The immunoassays described will be valuable for further studies on the synthesis and secretion of these proteins during mammary involution.
Assuntos
Bovinos/fisiologia , Glicoproteínas/análise , Lactoferrina/análise , Lactoglobulinas/análise , Glândulas Mamárias Animais/metabolismo , Período Pós-Parto/fisiologia , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Glândulas Mamárias Animais/fisiologia , GravidezRESUMO
Sixteen Holstein bull calves were used to evaluate effects of increasing blood BHBA, as a consequence of ruminal development, on response of peripheral blood mononuclear cells to mitogenic stimulation. Calves were blocked by date of birth and assigned to weaning at 35 or 49 d of the study. Calves began the study at 4 d of age. Milk replacer was fed at 10% of BW to d 7 prior to weaning; thereafter, milk replacer offered was reduced by 50%. Calf starter was offered from d 1. Blood was sampled at wk 0, 2, 4, 6, 8, and 10 at 4 h after the a.m. feeding. Blood glucose declined, and blood BHBA increased, as calf starter intake increased. Blood BHBA increased at weaning in each treatment group and exceeded 1 mM during the week of weaning. Responses of peripheral blood mononuclear cells to stimulation with concanavalin A, pokeweed mitogen, or phytohemagglutinin were unaffected by increasing blood BHBA and increased with age. Increased concentration of blood BHBA in young calves from increased starter intake did not impair immune response.
Assuntos
Bovinos/sangue , Bovinos/crescimento & desenvolvimento , Hidroxibutiratos/sangue , Leucócitos Mononucleares/fisiologia , Mitógenos/farmacologia , Ácido 3-Hidroxibutírico , Envelhecimento/sangue , Animais , Animais Recém-Nascidos/sangue , Glicemia/metabolismo , Masculino , Fito-Hemaglutininas/farmacologia , Mitógenos de Phytolacca americana/farmacologia , Rúmen/crescimento & desenvolvimento , DesmameRESUMO
1. Lactoferrin was isolated from bovine mammary secretions collected during the nonlactating period. 2. A method utilizing heparin-agarose affinity chromatography was more efficient for purifying lactoferrin than a method including gel filtration, ion exchange chromatography and a second gel filtration. 3. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that the purified lactoferrin was composed of two protein bands of apparent mol. wt. of 83,000 and 87,000. 4. Digestion with endoglycosidase H resolved the lactoferrin into two lower mol. wt. bands of 78,000 and 81,000. 5. The biochemical differences between the forms of lactoferrin are not exclusively due to differences in endoglycosidase H-sensitive oligosaccharide composition.
Assuntos
Lactoferrina/isolamento & purificação , Lactoglobulinas/isolamento & purificação , Glândulas Mamárias Animais/metabolismo , Sequência de Aminoácidos , Animais , Bovinos , Cromatografia de Afinidade , Cromatografia em Gel , Feminino , Dados de Sequência Molecular , Peso MolecularRESUMO
1. A non-radioisotopic method utilizing a biotin-avidin approach was used to characterize lactoferrin binding to the clonal MAC-T bovine mammary epithelial cell line. 2. Binding of lactoferrin to MAC-T cells and isolated membranes was specific and saturable. 3. Unlabeled lactoferrin competed for and displaced biotin-labeled lactoferrin from binding sites on mammary epithelial cells. In contrast, unlabeled transferrin did not compete. 4. Scatchard analysis of lactoferrin binding to MAC-T cell crude membranes was nonlinear, revealing two classes of binding sites with association constants (Ka) of 2.36 x 10(7) and 3.36 x 10(6) M-1. 5. Binding of lactoferrin to MAC-T cells may be associated with the initial events which result in decreased MAC-T cell proliferation.
Assuntos
Lactoferrina/metabolismo , Glândulas Mamárias Animais/metabolismo , Animais , Avidina , Biotina , Bovinos , Divisão Celular/fisiologia , Linhagem Celular , Membrana Celular/metabolismo , Células Epiteliais , Epitélio/metabolismo , Feminino , Imuno-Histoquímica/métodos , Glândulas Mamárias Animais/citologia , Ligação ProteicaRESUMO
Eight Jersey cows free of intramammary infection (IMI) with major mastitis pathogens were intramammarily infused with interleukin (IL)-1, IL-2, or phosphate-buffered saline (PBS) after the last milking prior to drying off. Rectal temperatures were monitored hourly through 6 hours after infusion and at 24-hour intervals thereafter. Quarter secretions were collected 7 days prior to drying off, at drying off, and on days 1, 2, 3, 4, 7, and 14 of the nonlactating period. Cows were slaughtered and mammary tissues were collected at 7 (3 cows) and 14 (5 cows) days after treatment. The infusion of 10 micrograms of IL-1 produced an elevation in rectal temperature that was significantly higher than that of cows receiving IL-2 or PBS at 4, 5, and 6 hours after treatment, whereas cows receiving 1.0 mg of IL-2 exhibited no change in rectal temperature. Somatic cell counts (SCC) in mammary glands infused with IL-1 or IL-2 remained significantly elevated over PBS-infused control glands through day 4 after treatment. Neutrophils predominated in secretions of IL-1-treated glands, and macrophages and lymphocytes predominated in IL-2-treated glands. The mammary involution process was accelerated by IL-2, and tissues exhibited reductions in alveolar epithelial and luminal areas and increases in connective tissue stroma and degree of leukocytosis compared with IL-1 and control glands. Concentrations of plasma cells producing IgG1, IgG2, IgA, and IgM also were greatest following IL-2 infusion. Results suggest that IL-2 is superior to IL-1 in stimulating an increase in mammary mononuclear cell populations and in accelerating involution during the early nonlactating period.
Assuntos
Interleucina-1/uso terapêutico , Interleucina-2/uso terapêutico , Glândulas Mamárias Animais/fisiologia , Mastite Bovina/prevenção & controle , Animais , Temperatura Corporal , Bovinos , Contagem de Células/veterinária , Feminino , Contagem de Leucócitos/veterinária , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/imunologia , Mastite Bovina/imunologiaRESUMO
Effects of bacterial virulence factors on bovine mammary cell structure and function are not well defined. In this study, we evaluated the influence of specific bacterial virulence factors on proliferation of a bovine mammary epithelial cell line. The MAC-T cells were cultured in the presence of medium only, Staphylococcus aureus alpha-toxin, Staph. aureus beta-toxin, Escherichia coli endotoxin, Streptococcus uberis capsule, or hyaluronidase. Cells were cultured in the presence of virulence factors for 48 h at 37 degrees C. The MAC-T cell proliferation was inhibited by all concentrations of endotoxin and alpha-toxin and by most concentrations of hyaluronic acid capsule and hyaluronidase > 7.8 micrograms/ml. Staphylococcus aureus beta-toxin had no effect on MAC-T cell proliferation. Virulence factors produced by mastitis pathogens may influence mammary epithelial cell proliferation in vivo, which could be important during the periparturient period, when mammary tissue undergoes rapid differentiation and growth.
Assuntos
Toxinas Bacterianas/farmacologia , Glândulas Mamárias Animais/citologia , Análise de Variância , Animais , Bovinos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Células Epiteliais , Epitélio/efeitos dos fármacos , Escherichia coli/patogenicidade , Feminino , Glândulas Mamárias Animais/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Streptococcus/patogenicidadeRESUMO
Development of the MAC-T bovine mammary epithelial cell line by stable transfection with simian virus-40 large T-antigen should greatly assist study of possible intrinsic (local) and extrinsic (systemic) factors regulating bovine mammary epithelial cell development, differentiation, and function. This study evaluated the influence of mammary secretion whey proteins alpha-lactalbumin (ALA), beta-lactoglobulin (BLG), lactoferrin (LF), transferrin (TF) and serum albumin (SA) on MAC-T cell proliferation in the absence and presence of 10% fetal bovine serum (FBS). Concentration of whey proteins in culture ranged from 0 to 625 micrograms/ml. MAC-T cell proliferation in the absence of FBS was significantly lower than in the presence of 10% FBS. Alpha-lactalbumin and LF significantly decreased MAC-T proliferation in both the absence and presence of 10% FBS. Transferrin significantly increased MAC-T cell proliferation only in the absence of FBS. There were no significant differences in MAC-T cell proliferation cultured in the presence of BLG or SA. These experiments illustrate the potential usefulness of MAC-T cells for the study of factors involved in mammary cell proliferation. Results identified ALA, LF and TF as possible intrinsic factors associated with regulation of mammary epithelial cell proliferation.
Assuntos
Glândulas Mamárias Animais/citologia , Proteínas do Leite/farmacologia , Animais , Bovinos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Transformada/efeitos dos fármacos , Lactalbumina/farmacologia , Lactoferrina/farmacologia , Lactoglobulinas/farmacologia , Glândulas Mamárias Animais/metabolismo , Albumina Sérica/farmacologia , Transferrina/farmacologia , Proteínas do Soro do LeiteRESUMO
Twenty-one Holstein calves (12 bulls, 9 heifers) were used to evaluate the effects of supplemental lactoferrin (0, 1, and 10 g/d) added to colostrum, milk, and milk replacer in a 56-d study. Calves fed lactoferrin (LF) weighed more during wk 2, 3, 4, 5, and 6 than control calves. Calves fed LF had increased preweaning daily weight gains and heart girth gains compared with calves not fed lactoferrin. Calves fed 1 g/d LF had a greater preweaning average daily gain than calves fed 10 g/d of lactoferrin. Hematocrit and serum Fe were unaffected by treatments. Calves were weaned when they had consumed 0.7 kg of calf starter grain for 2 consecutive d and were at least 28 d of age. All calves were weaned by 35 d of age, regardless of starter intake. Calves fed LF consumed more calf starter grain during the preweaning period and met weaning criteria at a younger age. This study indicates that supplementing calf diets with LF is advantageous to calf performance.
Assuntos
Bovinos/crescimento & desenvolvimento , Lactoferrina/administração & dosagem , Ração Animal , Animais , Bovinos/fisiologia , Colostro , Suplementos Nutricionais , Feminino , Coração/crescimento & desenvolvimento , Hematócrito , Ferro/sangue , Masculino , Leite , Desmame , Aumento de Peso/efeitos dos fármacosRESUMO
The specific, high-affinity binding of the avian oviduct progesterone receptor (PR) with target-cell nuclei and chromatin has been shown to involve DNA complexed with specific chromatin acceptor proteins. One of these chromatin acceptor proteins has been partially purified and found to be a small hydrophobic protein with a broad pI of 5.0-6.0 [Goldberger, A., & Spelsberg, T. C., (1988) Biochemistry 27, 2103-2109]. This paper describes the final purification over 100,000-fold to apparent homogeneity of this candidate PR acceptor protein, termed the receptor binding factor 1 (RBF-1). When the avian genomic DNA is bound by RBF-1, saturable, high-affinity (KD approximately 2 x 10(-9) M) binding sites for PR are generated. RBF-1 has a unique, hydrophobic N-terminal sequence. The PR binding to the RBF-1-DNA complexes is shown to be dependent on an intact activated PR with which excess nonradiolabeled PR can compete. By use of a new, highly specific monoclonal antibody (mAb) to the RBF-1 with Western immunoblotting, RBF-1 was shown to be localized in the nucleus and to be tissue and species specific. Selective removal of the chromatin proteins containing RBF-1 results in the loss of the highest affinity class of PR binding sites. A second class of residual PR binding sites remains in the nucleoacidic protein (NAP), a complex of proteins more tightly bound to the DNA. This class of PR binding activity has been classified as the RBF-2. The RBF-1 is estimated to be 0.03% of the total chromatin protein with about 1.2 x 10(5) molecules/diploid cell.
Assuntos
Proteínas Aviárias , Proteínas de Transporte/isolamento & purificação , Cromatina/química , Proteínas de Ligação a DNA/isolamento & purificação , Oviductos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Sequência de Aminoácidos , Animais , Ligação Competitiva , Western Blotting , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Galinhas , DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Dados de Sequência Molecular , Receptores de Progesterona/imunologiaRESUMO
This study was designed to determine whether intramammary infusion of recombinant bovine interleukin-1 beta or interleukin-2 had any adverse influence on bovine mammary function during the early non-lactating period. Mammary glands of eight Jersey cows were infused with either 10 micrograms of interleukin-1 beta or 1.0 mg of interleukin-2 following abrupt cessation of milking. Mammary secretions from each gland were collected from cows frequently during early involution and evaluated for changes in secretion composition. Percentage of milk fat and solids-not-fat during the experimental period was variable for all treatments. Percentage of protein increased throughout the study for all treatments, but mammary glands treated with interleukin-1 beta had higher protein percentages. All interleukin-treated mammary glands had lower concentrations of lactose than controls. Mammary secretions from interleukin-1 beta treated glands had higher concentrations of lactoferrin at 7 and 14 days of involution. Similarly, mammary secretions from interleukin-2 treated glands had higher concentrations of serum albumin on day 3 of involution and throughout the remainder of the study. Concentration of citrate and the citrate: lactoferrin molar ratio generally decreased throughout the study for all treatment groups. Concentration of alpha-lactalbumin in mammary secretions decreased throughout the study and was not different between treatment groups. Though significant changes in mammary secretion composition due to the presence of cytokines were observed in this study, resulting in an apparent acceleration of involution, there was no indication that these changes adversely affected normal bovine mammary function during the early non-lactating period.
Assuntos
Bovinos/metabolismo , Citocinas/farmacologia , Glândulas Mamárias Animais/metabolismo , Leite/química , Leite/metabolismo , Animais , Bovinos/fisiologia , Citocinas/efeitos adversos , Feminino , Interleucina-1/farmacologia , Interleucina-2/farmacologia , Lactação , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/fisiologia , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologiaRESUMO
There has been exciting progress in the understanding of the mechanism of action of steroid hormones. The structures and functions of the various receptor protein domains as well as the various domains of steroid-regulated genes, including steroid response elements, are currently being elucidated. The roles of transcription factors in the steroid-altered regulation of gene transcription are just being defined. The nature of the nuclear acceptor sites, i.e. nuclear-binding sites, for steroid receptors are under investigation. The composition, location, and function of these nuclear acceptor sites for steroid receptors is crucial for understanding the mechanism of steroid regulation of gene expression. Possible roles of specific, DNA-binding, chromatin proteins in these acceptor sites have been suggested. A very rapid action of steroids on the expression of proto-oncogenes that code for nuclear regulatory proteins has recently been described. Using this information, we have proposed a novel steroid action model utilizing "regulatory genes" whereby the steroids would rapidly alter the expression of regulatory genes (early genes) whose protein products would return to the nucleus to regulate the expression of structural genes (late genes). The latter would occur via binding of these regulatory proteins (e.g. transcription factors) to the steroid-regulatory elements neighboring these late genes. This model would explain many of the characteristics reported from many laboratories on the action of steroid hormones on gene expression.
Assuntos
Estrogênios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Genes Reguladores , Progesterona/farmacologia , Receptores de Esteroides/fisiologia , Animais , Sítios de Ligação , Cromatina/metabolismo , Humanos , Modelos Biológicos , Receptores de Estrogênio/análise , Receptores de Estrogênio/fisiologia , Receptores de Progesterona/análise , Receptores de Progesterona/fisiologia , Receptores de Esteroides/metabolismo , Fatores de Transcrição/fisiologiaRESUMO
Lactoferrin is a milk protein that exhibits broad-spectrum antimicrobial properties. Previous studies indicated that supplemental lactoferrin may alter the microbial populations in the gut of nonruminants and increase preweaning weight gains in calves. In the present study, 40 Holstein calves were used to examine the effects of supplemental lactoferrin (0, 1, 2, or 3 g/d) on health, growth, and feed intake from 3 d of age to 2 wk postweaning. Lactoferrin was mixed and fed with a nonmedicated milk replacer. Calves were housed in individual pens and offered a textured, nonmedicated starter and water for ad libitum consumption. Body weight and heart girth were measuredweekly. Intakes of milk replacer and starter were determined daily. Fecal consistency was monitored three times per week. Calves were weaned when they met certain criteria based on body weight gain and starter intake. Preweaning fecal score responded quadratically, with the group fed 1 g/d of lactoferrin having the lowest score. Overall and preweaning number of days medicated responded in the same manner as fecal score. Preweaning average daily gain and gain-to-feed ratio increased linearly with lactoferrin supplementation, whereas postweaning gain-to-feed ratio decreased linearly with lactoferrin. Overall average daily heart girth gain increased linearly with lactoferrin. Body weight, weaning age, and dry matter intake were not different among treatments. Based on the observed improved gain-to-feed ratios, increased average daily gains, improved fecal scores, and reduced morbidity in preweaned calves, it appears that lactoferrin may be a beneficial supplement in the diets of neonatal calves prior to weaning.