Efficacy of intramammary infusion of ceftiofur hydrochloride at drying off for treatment and prevention of bovine mastitis during the nonlactating period.

This study evaluated the efficacy of intramammary infusion of ceftiofur hydrochloride for the treatment of intramammary infections present at the last milking of lactation and for prevention of new intramammary infections during the nonlactating period. Cows were randomly assigned to five treatments (untreated negative control, 125, 250, and 500 mg of ceftiofur, and a positive control group receiving 300 mg cephapirin benzathine). A dose of 125 mg of ceftiofur per mammary quarter was effective for treatment of existing infections present at the time of milk cessation, but only the 500-mg dose of ceftiofur per mammary quarter was effective for both treatment of existing intramammary infections at the time of milk cessation and for prevention of new intramammary infections during the nonlactating period.

Extended ceftiofur therapy for treatment of experimentally-induced Streptococcus uberis mastitis in lactating dairy cattle.

Streptococcus uberis is an important cause of mastitis in dairy cows throughout the world, particularly during the dry period, the period around calving, and during early lactation. Strategies for controlling Strep. uberis mastitis are poorly defined and are currently inadequate. Objectives of the present study were to evaluate efficacy of ceftiofur, a new broad-spectrum cephalosporin antibiotic, for treatment of experimentally induced Strep. uberis intramammary infections (IMI) in lactating dairy cows during early lactation and to determine whether extended therapy regimens enhanced efficacy of ceftiofur. Efficacy of extended ceftiofur intramammary therapy regimens was investigated in 37 mammary quarters of 23 dairy cows that developed clinical mastitis following experimental infection with Strep. uberis during early lactation. Cows that developed clinical mastitis during the challenge period were allocated randomly to 3 groups representing 3 different ceftiofur treatment regimens: 2-d (n = 7 mammary quarters), 5-d (n = 16 mammary quarters), and 8-d (n = 14 mammary quarters) treatment regimens. For all groups, 125 mg of ceftiofur hydrochloride was administered via intramammary infusion. A bacteriological cure was defined as an experimentally infected quarter that was treated and was bacteriologically negative for the presence of Strep. uberis at 7, 14, 21, and 28 d posttreatment. Percentage of Strep. uberis IMI eliminated was 43, 88, and 100% for the 2-, 5-, and 8-d ceftiofur treatment regimens, respectively. Both the 5- and 8-d ceftiofur extended therapy treatment regimens had significantly higher bacterial cure rates than the standard 2-d ceftiofur treatment regimen. The bacterial cure rate of the 8-d ceftiofur extended therapy group was marginally better (P = 0.052) than the 5-d ceftiofur extended therapy group. Results of this study indicate that ceftiofur therapy was effective for eliminating Strep. uberis experimental IMI, and 5- and 8-d extended ceftiofur therapy regimens were more effective than the standard 2-d treatment.

Efficacy of extended ceftiofur intramammary therapy for treatment of subclinical mastitis in lactating dairy cows.

Little research has focused on treatment of cows with subclinical mastitis during lactation. Ceftiofur is a new broad-spectrum, third-generation cephalosporin antibiotic for veterinary use that inhibits bacterial cell wall synthesis by interfering with enzymes essential for peptidoglycan synthesis. Ceftiofur should be effective against a wide range of contagious and environmental mastitis pathogens. Objectives of the present study were to evaluate the efficacy of ceftiofur for treatment of subclinical mastitis in lactating dairy cows, and to determine if extended therapy regimens enhanced efficacy of ceftiofur. Holstein and Jersey dairy cows (n = 88) from 3 dairy research herds were used. Cows were enrolled in the study based on milk somatic cell counts >400,000/mL and isolation of the same mastitis pathogen in 2 samples obtained 1 wk apart. Cows with one or more intramammary infections (IMI) were blocked by parity and DIM and allocated randomly to 1 of 3 different ceftiofur treatment regimens: 2-d (n = 49 IMI), 5-d (n = 41 IMI), and 8-d (n = 38 IMI) treatment regimens. For all groups, 125 mg of ceftiofur hydrochloride was administered via intramammary infusion. Eighteen cows with 38 IMI were included as an untreated negative control group. A bacteriological cure was defined as a treated infected mammary quarter that was bacteriologically negative for the presence of previously identified bacteria at 14 and 28 d after the last treatment. Efficacy of ceftiofur therapy against all subclinical IMI was 38.8, 53.7, and 65.8% for the 2-, 5-, and 8-d ceftiofur treatment regimens, respectively. Four of 38 (10.5%) IMI in control cows were cured spontaneously without treatment. All 3 ceftiofur treatment regimens were significantly better than the negative control, and the 8-d extended ceftiofur treatment regimen treatment group was significantly better than the standard 2-d treatment group. Pathogen groups had significantly different cure rates from one another. The cure rate for the 8-d extended ceftiofur treatment regimen was 70% for Corynebacterium bovis, 86% for coagulase-negative Staphylococcus species, 36% for Staph. aureus, 80% for Streptococcus dysgalactiae ssp. dysgalactiae, and 67% for Strep. uberis.

A dose-response study of melengestrol acetate on feedlot performance and carcass characteristics of beef steers.

The dose response of melengestrol acetate (MGA) on ADG (kg/d) and gain efficiency (gain/DMI, g/kg) was estimated in beef steers fed a finishing diet under commercial feedlot conditions. Melengestrol acetate is not approved for use in steers as a feed additive. The study design was five blocks of four pens (each pen was assigned a dose of MGA) with 166 to 200 steers per pen. Melengestrol acetate was fed to steers at 0 (n = 899, five pens), 0.1 (n = 900, five pens), 0.2 (n = 899, five pens), and 0.4 (n = 900, five pens) mg of MGA/steer daily. Pens within a block were slaughtered on the same day. Blocks 1 through 5 were fed MGA for 123, 122, 116, 124, and 138 d, respectively. The experimental unit was a pen of steers, and blocking was based on source of steers. The ADG was 1.81, 1.85, 1.80, and 1.83 kg/d for steers fed 0, 0.1, 0.2, and 0.4 mg MGA per day, respectively. For ADG, the dose was significant, but neither linear nor quadratic effects were significant. Compared with steers of the control group, ADG was greater for steers fed 0.1 mg MGA (P < 0.01). Feed efficiencies were 170, 173, 171, and 172 g/kg for steers fed 0, 0.1, 0.2, and 0.4 mg MGA/d, respectively; however, no effects of dose (P = 0.19) or linear (P = 0.21) or quadratic (P > 0.60) effects were observed. There was no evidence for either positive or negative effects of MGA on DMI, hot carcass weight, dressing percent, quality grade, yield grade, back fat thickness, marbling score, longissimus muscle area, and incidence of dark cutter carcasses in response to feeding MGA to steers at doses of 0.1, 0.2, and 0.4 mg daily. The incidence of buller behavior (0.43 to 1.11%) was low and did not permit an accurate test of the clinical observations that feeding MGA to steers decreases the occurrence of buller steers. Melengestrol acetate fed to finishing beef steers produced small improvements in growth performance (ADG, 2.2%) at the 0.1 mg MGA dose, but none of the doses examined produced improvement in carcass quality or yield grade measurements.

Evaluation of models of acute and subacute acidosis on dry matter intake, ruminal fermentation, blood chemistry, and endocrine profiles of beef steers.

Crossbred steers (n = 20; 316 +/- 4 kg BW), each fitted with a ruminal cannula, were used to evaluate the effects of acute acidosis (AA) and subacute acidosis (SA) on DMI, ruminal fermentation, blood chemistry, and endocrine profiles. Animals were blocked by BW and assigned to treatments including 1) intraruminal (via cannula) steam-flaked corn (3% of BW; AA); 2) intraruminal dry-rolled wheat:dry-rolled corn (50:50; 1.5% of BW; SA); 3) offering forage-adapted steers ad libitum access to a 50% concentrate diet (AA control; AC); and 4) offering 50% concentrate diet-adapted steers ad libitum access to a 50% concentrate diet (SA control; SC). Samples of ruminal fluid and whole blood were collected on the day of the challenge (d 0) and 3, 7, 10, and 14 d after the challenge. Daily DMI responded quadratically (P < 0.01) through d 7 for AA and SA steers and increased linearly (P < 0.01) for AC steers. Dry matter intake by AA steers reached a nadir (< 3 kg/d) on d 3 and gradually increased to a level similar to other treatments (7 kg/d) by d 10, whereas DMI by SA steers increased through d 3. Blood pH, bicarbonate, base excess, and total CO2 were decreased (P < 0.03) for AA steers and increased (P < 0.03) for SC steers through d 7. Ruminal pH decreased quadratically (P < 0.01) in AA and AC steers and increased (P = 0.01) in SA steers through d 7. Ruminal total lactate concentration and osmolality responded quadratically (P < 0.01) for AA and AC steers. Ruminal total lactate peaked on d 3 for AA steers and on d 0 for AC and decreased to basal concentrations by d 7. Plasma NEFA concentration increased (P < 0.04) on d 3 and 7 for AA steers. Serum Na decreased (P < 0.05) on d 0 for AA and SA steers and on d 7 and 14 for AA steers. Serum P decreased (P = 0.01) for AA steers through d 7 and decreased quadratically (P = 0.01) for AC steers through d 7. Serum albumin and cholesterol decreased (P < 0.02) for AA and AC steers through d 7. Area under the GH curve decreased (P = 0.02) for AA and AC steers through d 7. Considerable variation was evident in the ability of an animal to cope with a carbohydrate challenge. Results of data modeling generally suggest that serum amylase activity, cholesterol and potassium concentrations, and plasma NEFA concentrations were useful in distinguishing between steers classified as experiencing subacute acidosis or not affected by a carbohydrate challenge.

Effects of Synovex-S and recombinant bovine growth hormone (Somavubove) on growth responses of steers: III. Muscle growth and protein responses.

We conducted this study to determine whether the growth responses of specific skeletal muscles in crossbred beef steers were differentially affected by treatment with recombinant bovine growth hormone (Somavubove, SbV, .1 mg/kg BW, i.m., daily), Synovex-S (200 mg progesterone + 20 mg 17-beta estradiol benzoate, SYN, ear implant), or a combination of the two. Starting body weights of steers averaged 182+/-1.8 kg. Five steers were used at this average BW to obtain data on weight and composition of individual muscles at d 0, and 20 other steers were assigned in equal numbers to control (C, no implant and placebo daily injection), SYN, SbV, and SYN + SbV treatment groups. After 56 d of treatment with placebo or growth promoters, complete rectus femoris (RF), triceps brachii (TB), supraspinatus (SS), psoas major (PM), and semitendinosus (ST) muscles were dissected, weighed, and then ground for determination of moisture, total protein, and fat. To calculate the average daily muscle wet weight, protein, and fat gains, the initial weight, protein content, and fat content of a muscle were subtracted from those obtained at slaughter and the difference divided by 56. Muscle weight was increased over C in TB and SS by SYN (P < .1); in TB by SbV (P < .09); and in RF (P < .05), TB (P < .03), and SS (P < .03) by SYN + SbV. Overall average daily wet tissue gain was increased over C by SbV + SYN (P < .05) in RF, TB, and SS. Average daily protein gain in RF and TB was increased by SYN (P < .1), SbV (P < .06), and SYN + SbV (P < .01) over that calculated for C. For RF, TB, and SS, average daily protein gain was greater (P < . 1) in SbV + SYN than that obtained with SbV or SYN alone. These data suggest that administration of growth promoters, such as somatotropin and Synovex, to cattle differentially affects growth characteristics in certain muscles and can have additive effects on protein gain when used together.

Use of the HIV-1 protease for excision of growth-hormone-releasing factor from synthetic and recombinant peptide precursors.

An autolysis-resistant mutant of the HIV-I protease was employed for removal of metabolically stabilized and highly bioactive analogues of bovine growth-hormone-releasing factor (bGRF) from their larger either synthetic or recombinant precursors. The N-terminal four amino acids in two selected model GRF analogues, Y1IDAIFTSSYRKVLAQLSARKLLQDILSRQVF32-OH (I; GRF32) and Y1IDAIFTSSYRKVLAQLSARKLLQDILSRQ30-OH (IA; GRF30), conform well to the specificity of the HIV-I protease for residues in the P1' to P4' positions of its peptide substrates. A variety of amino acids were tried in the N-terminal extension (positions P4-P1) to fit the protease substrate specificity for the 8 amino acids in positions P4-P4'. A synthetic precursor of I, extended N-terminally with RQVF-, a sequence representing the four C-terminal residues in I, was effectively cleaved by the protease at the Phe-1-Tyr1 bond (... RQVF-decreases-YIDA ...) to release GRF32. However, when several soluble fusion proteins linked to GRF32 by the RQVF sequence were expressed in Escherichia coli, attempts to cleave out the core GRF32 met with variable, and only limited, success. By random mutagenesis in a propeptide segment, [MGQSVAQVF]-decreases-GRF30, (II) was identified as a construct that showed reasonably high-level expression in E. coli and was effectively processed by the HIV-I protease. A yield of 5 mg of pure GRF30 was obtained/litre of culture medium after a single HPLC purification step.

Effects of Synovex-S and recombinant bovine growth hormone (Somavubove) on growth responses of steers: I. Performance and composition of gain.

The influence of Synovex-S (SYN) ear implant (200 mg progesterone and 20 mg estradiol benzoate) and Somavubove (SbV) recombinant bovine growth hormone (.1 mg/kg BW i.m., daily) on live animal performance, tissue growth, and the partitioning of energy gain was determined using a slaughter-balance protocol with 25 young MARC II x (Angus-Hereford crossbred) beef steers (initial BW 182 +/- 1.8 kg). Following 21 d of adjustment to individual pens and to a diet of 80% concentrate and 20% corn-grass (1:1) silages, five groups of five steers per group were assigned to initial slaughter or a 2 x 2 factorial arrangement of treatments of CTL (no implant + daily placebo i.m. injection of bicarbonate-saline), SYN (implant + placebo), SbV, or SYN + SbV and slaughtered at 56 d on treatment. Steers were fed (per kilogram BW.75 daily) 20 g of CP and 252 Kcal of ME and consumed 5.5 +/- .07 kg/d DM across treatments. Empty body and carcass gains were affected (SYN, P < .01; SbV, P < .01) by treatments (CTL, SYN, SbV, and SYN + SbV: 1.26, 1.43, 1.63, 1.78 kg/d, SEM = .05, and .78, .97, .97, 1.08 kg/d, SEM = .04, respectively). Noncarcass gain was .45, .48, .60, and .60 kg/d (SEM = .03; SbV, P < .01). For empty body, both protein and water gains were greater for SYN-implanted steers (P < .05) than for steers not implanted and for SbV-injected steers (P < .01) than for placebo-injected steers. Treatments did not influence the efficiency of energy gain. The proportional amount of energy deposited as protein was greater (P < .01) for SbV-injected steers than for placebo-injected steers. The proportional amount of protein deposited was not influenced by SYN (P > .10); however, means were numerically greater for SYN-implanted steers than for steers not implanted, the largest mean being for the SYN + SbV treatment group. Somavubove increased (P < .01) the efficiency of energy deposited as protein in both the empty body and carcass compared with steers not receiving SbV. Efficiency of energy deposited as protein in the empty body tended to be greater (P < .10) for SYN-implanted steers than for steers not implanted. The efficiency with which total feed energy was deposited as protein in empty body was 10% greater for the SYN group than for the CTL group, 21% greater for the SbV group than for the CTL group, and 37% greater for the combined SYN + SbV treatment than for the CTL group. The data from this study are interpreted to indicate that SYN and SbV act in an additive manner to improve growth and protein deposition in young growing steers.

Effects of Synovex-S and recombinant bovine growth hormone (Somavubove) on growth responses of steers: II. Muscle morphology and proximate composition of muscles.

Twenty crossbred beef steers (initial BW 182 +/- 1.8 kg) were used in a 2 x 2 factorial to determine the effects of implantation with Synovex-S (SYN; 20 mg 17-beta estradiol benzoate + 200 mg progesterone, ear implant) and administration of recombinant bovine growth hormone (Somavubove SbV, .1 mg.kgBW-1.d-1, i.m.) on the morphology of six muscles (longissimus, psoas major, supraspinatus, triceps brachii, semitendinosus, rectus femoris) of growing steers. Implantation with SYN decreased the percentage distribution of FOG fibers and increased FG fibers in the supraspinatus and rectus femoris muscles (P < .05). Steers treated with SYN had a larger area of SO and FG fibers in the psoas major muscle (P < .05). The administration of SbV decreased the percentage distribution of FOG fibers and increased FG fibers in the rectus femoris muscle (P < .05). Steers administered SbV had larger SO, FOG, and FG fibers in the psoas major muscle and SO fibers in the supraspinatus and semitendinosus muscles (P < .05). The combined administration of SYN and SbV had minimal, if any, effect on the percentage distribution of fiber types (P > .05) but increased (P < .05) the fiber areas of all muscles (18.5 to 54.8%) except the rectus femoris (P > .05). Proximate composition of the muscles was generally not affected (P > .05) by any of the treatments. The only observations were decreases in fat content for psoas major and rectus femoris muscles as a result of the combined administration of SYN and SbV. These results indicate that both growth-promoting agents, SYN and SbV, have potential to increase muscle fiber size, but muscles respond differently to the administrations of SYN and SbV. However, when SYN and SbV are administered in combination, the combined effects result in an additive increase in muscle fiber hypertrophic response.

Regulation of the gene expression of glucose transporter in liver and kidney of lactating cows by bovine growth hormone and bovine growth hormone-releasing factor.

Our objective was to study the effects of recombinant bovine growth hormone and bovine growth hormone-releasing factor on gene expression of glucose transporters in the liver and kidney of lactating cows. Primiparous cows received 29 mg/d of bovine growth hormone or 12 mg/d of bovine growth hormone-releasing factor by continuous intravenous infusion or no treatment (control) from 118 to 181 d postpartum. Growth hormone or growth hormone-releasing factor did not influence the mRNA abundance of the liver-type glucose transporter in the liver or kidney. Similarly, neither growth hormone-releasing factor nor growth hormone altered the mRNA abundance of the erythrocyte-type or the intestinal-type glucose transporter in the kidney, but large individual differences were observed in the mRNA abundance of the intestinal-type glucose transporter in liver.

Hormonal and nutritional modulation of hepatic arginase activity in growing cattle.

The hormonal and nutritional modulation of hepatic arginase activity (HARG) was characterized in growing cattle in two studies. In the first study, 20 steers (initial weight, 182 +/- 2 kg) were assigned in equal numbers to either Synovex-S (SYN) (ear implant), recombinant bovine somatotropin (Somavubove; SbV; 0.1 mg/kg intramuscularly daily), SYN + SbV, or nothing (control). Steers were individually fed, for 56 d, a concentrate (80% diet dry matter [DM]) and silage (20% diet DM) diet providing 20 g of crude protein (CP) and 252 kcal metabolizable energy (ME) per kg body weight0.75. On Day 57, samples of liver were obtained at slaughter and subsequently assayed for HARG by the incubation of a tissue homogenate for 2 hr with 250 mM arginine, with and without Mn2+ and heat activation, and the measurement of the resulting urea. HARG was uniformly increased by divalent cation (Mn2+) and heating. SYN had no effect on HARG, whereas SbV treatment resulted in an overall 34% decrease in HARG. Plasma urea nitrogen (PUN) was decreased by SbV but not consistently affected by SYN. In the second study, 16 steers (avg. initial weight, 284 +/- 5 kg) were initially fed a concentrate basal diet consisting of 11% CP and 1.96 Mcal ME for 21 d. Steers were then assigned to one of four dietary treatments (6.4 kg DM/hr per day) in a factorial arrangement of high and low CP (8 and 14%) and two levels of energy (1.96 and 2.67 Mcal ME/kg of diet DM) for 210 d and slaughtered. HARG and PUN were higher in steers fed 14% CP but were lower at each level of CP fed at the higher level of ME. The data suggest that hormonal repartitioning compounds and diet composition may modulate nitrogen metabolism by affecting the activity of arginase in the liver as well as by affecting the total content of arginase in association with changes in organ size.

Preparation, characterization, and in vivo evaluation of an oil suspension of a bovine growth hormone releasing factor analog.

Pharmacia & Upjohn Inc. has discovered a superior bovine growth hormone releasing factor analog, [IIe2,Ser8,28,Ala15,Leu27,Hse30] bGRF (1-30)-NH-ethyl, acetate salt (U-90699F), for enhancement of animal growth. This report delineates the preparation, characterization, and in vivo evaluation of a U-90699F oil suspension. The oil suspension formulation was selected because of its simplicity, inexpensiveness, and ability to produce sustained U-90699F release. 40% U-90699F monomers were incorporated into Miglyol oil with acceptable injectability. Both reversed-phase-high-pressure liquid chromatography (RP-HPLC) and Fourier transform infrared spectroscopy (FTIR) were utilized to evaluate its chemical and structural stability. This suspension formulation demonstrated no significant changes in concentration as determined by RP-HPLC for 10 weeks at both 25 and 39 degrees C. The U-90699F dispersed in oil also showed no signs of structural conversion from alpha-helix to beta-sheet as monitored by FTIR. However, there was an increase in alpha-helix/disordered coil structure after initial drug incorporation. The suspension was subcutaneously administered to Holstein steers. Areas under the serum somatotropin concentration curve were used to determine the duration of action. It was found that the suspension was able to effectively elevate serum somatotropin for at least 14 days.

Regulation of glucose transporter gene expression in mammary gland, muscle, and fat of lactating cows by administration of bovine growth hormone and bovine growth hormone-releasing factor.

Primiparous cows received 29 mg of bovine growth hormone (bGH)/d, or 12 mg of bovine growth hormone-releasing factor (bGHRF)/d by continuous i.v. infusion, or no treatment (controls) from 118 to 181 d postpartum. Compared with controls, bGHRF and bGH did not influence the amount of erythrocyte-type glucose transporter (GLUT1) protein in the mammary gland; however, GLUT1 mRNA was increased (P < .01) by bGHRF, but not by bGH. The insulin-responsive glucose transporter (GLUT4) mRNA in skeletal muscle was decreased by 44% (P < .05) as a result of bGH treatment, but there was no significant effect of bGHRF. The GLUT4 mRNA was barely detectable in the omental fat of control cows and became undetectable in bGH-and bGHRF-treated cows. The results of the present study indicate that bGH and bGHRF may increase glucose availability to the mammary gland by regulating glucose transporter expression in skeletal muscle and omental fat. Our data also indicate that the galactopoietic action of bGHRF may not be mediated solely through GH.

Body composition and metabolic profiles associated with puberty in beef heifers.

Rapid growth large frame (RL, n = 61) or average growth medium frame (AM, n = 71) biotype heifers fed to achieve either moderate (MOD, .6 kg/d) or high ADG (HI, 1.0 kg/d) were used to determine whether puberty occurs at similar body composition or metabolic status. A heifer was considered pubertal after being detected in estrus and then forming a functional corpus luteum. Live animal estimates of body composition and blood samples for assessment of metabolic status were taken at 13 +/- .2 d after estrus for all heifers. Body composition and metabolic status were assessed every 56 d from 7 mo of age until puberty in a subset of 80 heifers representing all biotype-diet combinations. At puberty, 32 of these 80 heifers were slaughtered and physical and chemical composition of the empty body were determined. High-gain diet heifers were younger, heavier, taller, and more muscular (all P < .01) at puberty than MOD heifers. Slaughter measurements paralleled live animal estimates; bodies of HI and RL heifers contained more (P < .01) carcass and noncarcass components than those of MOD and AM heifers, respectively. Carcasses of RL and HI heifers were more (P < .05) muscular and fatter than AM and MOD heifers. At puberty, HI heifers had a greater (P < .01) mass of moisture, fat, and fat-free organic matter (FFOM) than MOD, whereas RL heifers had more moisture, ash, and FFOM than AM. Percentage of fat was greater (22.1 +/- 1.0 vs 1.0 vs 19.1 +/- 1.0; P < .05) and percentage of moisture was less (55.4 +/- .6 vs 58.1 +/- .6; P < .01) in bodies of HI than in those of MOD heifers. Concentrations of blood urea nitrogen and insulin were greater (P < .05) in HI than in MOD heifers. Diet did not influence concentration of IGF-I or glucose, and metabolic markers were unaffected by biotype. No dramatic changes in body composition or metabolic signals were detected before puberty. Puberty did not occur at similar body composition or metabolic status in all heifers.

Comparison of growth hormone-releasing factor and somatotropin: body growth and lactation of primiparous cows.

Growth hormone-releasing factor is the main endogenous stimulator of somatotropin secretion. Our objective was to compare the effects of recombinant growth hormone-releasing factor and recombinant bST on somatotropin secretion, mammary function, and body composition of lactating, primiparous dairy cows. Cows (118 d of lactation) served as uninfused controls or were infused for 63 d with 12 mg/d of releasing factor or with 29 mg/d of bST. These doses elevated somatotropin in serum to concentrations of similar magnitude. The releasing factor and bST each similarly increased milk yield, yield of milk components, weight of most organs, mobilization of adipose tissue, accretion of lean tissue in the carcass, and metabolic activity (RNA) of mammary tissue. Relative to controls, neither releasing factor nor bST significantly affected cell numbers (DNA) in mammary glands or concentrations of plasmin in milk. None of the variables measured provided evidence for galactopoietic effects of releasing factor independent of somatotropin.

Comparison of growth hormone-releasing factor and somatotropin: lipid and glucose metabolism in dairy cows.

Lactating, primiparous Holstein cows were continuously infused for 63 d with either recombinant growth hormone-releasing factor or recombinant bST or were not infused (control). The releasing factor and bST treatments reduced fat synthesis from acetate and lipoprotein lipase activity in omental adipose tissue. Also, both treatments increased hormone-sensitive lipase activity per gram of adipose tissue and reduced fatty acid esterification per milligram of protein in adipose tissue. Protein concentration in adipose tissue with both treatments was greater than that of the control, although the protein concentration was less in adipose tissue from cows treated with the releasing factor than from those treated with bST. In mammary tissue, releasing factor increased fat synthesis from acetate more than did bST treatment, but percentages of fat or short-chain fatty acids in milk were not different between treatments, nor were differences significant between treatments and control for fatty acid esterification or lipoprotein lipase activity in mammary tissue or gluconeogenesis and fatty acid esterification in liver. We conclude that protein concentration was lower in omental adipose tissue of cows treated with releasing factor than that in tissue of cows treated with bST, although both treatments similarly suppressed synthesis of fat from acetate and activity of lipoprotein lipase.

Comparison of growth hormone-releasing factor and somatotropin: the somatotropic axis in lactating primiparous cows.

Our objective was to compare the effects of recombinant bovine growth hormone-releasing factor and recombinant bST on the somatotropic cascade in lactating dairy cows. Primiparous cows were killed after 63 d of continuous daily infusion with 12 mg of releasing factor or 29 mg of bST or no infusion (controls). Both hormone infusions similarly increased mean concentration of somatotropin in serum, but pulsatility of somatotropin in serum was greater for cows given releasing factor. Both hormone infusions increased the amounts of IGF-I in serum, IGF-I mRNA in liver, and IGF-binding protein-3 in serum and decreased IGF binding protein-2 in serum, but these effects were less for cows given releasing factor than for those given bST. Both infusions decreased the number of free binding sites for IGF-I in mammary tissue. In liver, treatment did not alter the abundance of mRNA for the somatotropin receptor or the number of free binding sites for somatotropin. Results suggest that endogenous somatotropin is less effective as an IGF-I secretagogue than is exogenous bST infused continuously, yet the releasing factor and bST increased milk yield similarly. We conclude that growth hormone-releasing factor stimulates milk synthesis mostly through the same mechanisms as bST, but that serum IGF-I alone is not a good indicator of the galactopoietic potency of the two hormones.

Comparison of growth hormone-releasing factor and somatotropin: thyroid status of lactating, primiparous cows.

Effects of recombinant bovine growth hormone-releasing factor and recombinant bST on thyroxine 5'-deiodinase activities of liver and mammary gland were studied for lactating cows. Beginning on d 118 of lactation, 30 primiparous Holsteins received continuous infusions of 12 mg/d of releasing factor or 29 mg/d of bST or served as uninfused controls for 63 d. Blood samples were collected on d 1, 29, and 57, and samples of whole milk were collected at the early afternoon milking on d -5, 30, and 58. Liver and mammary tissue samples were obtained at slaughter on d 63. Infusion of releasing factor and bST decreased serum concentration of triiodothyronine by 10% and the ratio of triiodothyronine to thyroxine in serum by 20%. Concentrations of circulating triiodothyronine reflected a 30% decrease in hepatic 5'-deiodinase activity in response to infusion with releasing factor and bST. In contrast, treatment with releasing factor and bST did not affect 5'-deiodinase activity in the mammary gland and did not alter triiodothyronine concentration in milk. Data suggest that releasing factor and bST increase the hypothyroid status of the lactating cow and maintain an euthyroid condition in the mammary gland, thus enhancing the metabolic priority of the mammary gland.

Long-term somatotropic and galactopoietic effects of a (1-30) ethyl amide analog of growth hormone-releasing factor.

Thirty-five lactating Holstein cows (165 +/- 8 DIM) received the following treatments for 96 d: uninfused controls; i.v. infusion of .9, 2.7, or 8.1 mg/d of Ile2, Ser8.28, Ala15, Leu27, Hse30-bovine growth hormone-releasing factor (1-30) ethyl amide; or i.v. infusion of 12 mg/d of recombinant Leu27, Hse45-bovine growth hormone-releasing factor (1-45) lactone. Concentrations of somatotropin in serum and SCM yield of cows infused with 1-30 releasing factor increased quadratically as the dose increased. Responses for somatotropin and SCM yield were quantitatively similar for cows infused with 2.7 and 8.1 mg of 1-30 or 12 mg of 1-45. While concurrently infused with the 1-30 or 1-45 as described, cows retained their ability to release somatotropin following an acute i.v. injection of 10 nmol/100 kg of BW of either growth hormone-releasing factor 1-30 or 1-45. Mean concentrations of IGF-I in serum increased similarly in magnitude for cows infused at all doses of 1-30 or 1-45. The 1-30 releasing factor generally increased IGF-binding protein-3, but had little effect on IGF-binding protein-2. The 1-45 releasing factor did not significantly affect either binding protein. Yield of SCM was correlated with serum concentrations of somatotropin, but not with IGF-I. Concentrations of NEFA in serum were elevated through 36 and 50 d in response to the highest doses of 1-30 and 1-45, respectively. Treatment did not affect DMI, BW, or body condition score.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of daily slaframine injection of salivary score, feed intake, ruminal pH, and circulating concentrations of somatotropin and insulin-like growth factor I.

In a randomized complete block design with repeated measures, ruminally cannulated crossbred beef steers (n = 24; 279 +/- 3.2 kg) had ad libitum access to a 90% concentrate diet and were injected daily with slaframine dichloride (SF) at doses of 0, 30, or 60 micrograms SF free-base/kg BW. On d 1, 2, 7, 14, and 21, salivary scores were determined hourly from -2 to 8 h relative to injection (0 h), and ruminal pH was measured at 0, 4, and 8 h. Feed intake was measured daily. Serum concentrations of somatotropin (ST) were measured in samples collected at 20-min intervals from -40 min to 8 h on d 2, 7, 14, and 21, and IGF-I was measured at 8 h. Mean salivary score increased with SF injection (P < .01; .4, 3.3, and 3.7 for 0, 30, and 60 micrograms of SF/kg BW, respectively), although there was a dose x day interaction (P < .01). Injection of SF reduced DMI (P < or = .01; 6.39, 4.95, and 2.64 kg of DM/d for 0, 30, and 60 micrograms of SF/kg BW, respectively). Mean ruminal pH was increased (P < .01); 6.03, 6.42, and 6.72 for 0, 30, and 60 micrograms of SF/kg BW, respectively). Steers administered 60 micrograms of SF/kg BW lost weight (P = .02; 15.1 and -20.3 kg for 0 and 60 micrograms of SF/kg BW, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)