The responses of lactating Holstein cows to daily administration of bovine somatotropin (bST) were measured at thermoneutrality (Tn) and under both constant and cycled heat-stress conditions to determine the relationship between thermal status and bST-induced shifts in milk production. All tests included a 5-d acclimation period at Tn (18 degrees C), followed by a 2-d increase in ambient temperature to 28.5 degrees C. After d 3, ambient temperature was cycled between 28.5 (day) and 25.5 degrees C (night) for 4 d. Daily injections with either 31 mg of bST or saline began on d 1 of the experiment. Milk production, feed intake, and respiratory rate (RR) were measured daily. Intraperitoneal, telemetric temperature transmitters were used for a continuous measure of core body temperature (T(core)). Blood samples were collected during each phase to evaluate the changes in serum chemistry in response to bST and heat stress. Following a 15-d recovery, cows were switched across injection treatments and the study was repeated. Milk production decreased by approximately 18.4% below the initial yield at Tn by the end of 7 d of heat challenge. Although a reduction in milk production occurred during heat stress in both groups, milk production was higher in bST-treated cows compared with control cows during periods of constant and cyclic heat. Likewise, bST treatment during the entire period increased the milk-to-feed ratio over the control level by approximately 11.3%. Plasma insulin-like growth factor 1 and serum nonesterified fatty acids accompanied the increased growth hormone level with bST treatment (approximately 122.0 and 88.8%, respectively), whereas plasma urea nitrogen was reduced by approximately 13.3% to reflect the shift to lipid metabolism. There was no difference in T(core) of the treatment and control groups at Tn. Both bST and control cows increased RR and T(core) above the Tn level by approximately 94.8 and 2.9%, respectively, during constant heat, with a greater increase in T(core) of bST-treated compared with control cows (approximately 0.6%). The increase in RR during heat stress preceded T(core) by 1 d for both groups. During cyclic heat, T(core) decreased by approximately 0.4% compared with constant heat in both the control and bST-treated groups. Bovine somatotropin treatment increased milk production similarly during the Tn and heat-stress periods, approximately 8.3% over the control; however, the bST-induced increase in milk-to-feed ratio was greatest during the continuous and cyclic heat-stress phases, approximately 16.2%. This increase occurred together with the elevation in T(core).
The objective was to evaluate whether addition of EAZI-BREED CIDR Cattle Inserts (CIDR) to the Ovsynch program increases first service pregnancy rate (PR) in lactating dairy cows. The study was conducted in 5 dairies in Central Mexico. Cows were inseminated from June through September, 2001. Within trial site and within parity, cows were assigned to either an Ovsynch (n=255) or an Ovsynch-CIDR group (n=255) for their first service. Ovsynch was initiated at 50±3 d postpartum with an injection of 100 μg of GnRH (2 mL, i.m.; CYSTORELIN), an injection of 25 mg of PGF2α (5 mL, i.m.; LUTALYSE Sterile Solution) 7 d later, a second 100 μg injection of GnRH 48 h later, and timed insemination 8 to 20 hours after the second GnRH injection. Ovsynch-CIDR cows received the same treatments but also received a CIDR Insert (1.38 g of progesterone) which was administered with the first GnRH injection and removed 7 d later at the PGF2α injection. Cows were palpated for pregnancy 40 to 45 d after timed insemination. An interaction between treatments and parity was detected (P=0.023). The interaction indicated that PR was increased for Ovsynch-CIDR compared to Ovsynch in primiparous cows (38.2% and 20%, respectively; P=0.024) but no differences were detected in multiparous cows (22.3% and 27.5%, respectively; P=0.375). A subset of cows (n=466) was classified as anestrus or cyclic based on progesterone concentrations of two blood samples collected 7 d prior to and at the first GnRH injection. For anestrous cows, PR was 18.8% for Ovsynch (6/32) and 18.4% for Ovsynch-CIDR (7/38). For cyclic cows, PR was 23.5% for Ovsynch (47/200) and 29.1% for Ovsynch-CIDR (57/196). Such effects were further subdivided according to parity but none were significant. Addition of CIDR increased first service pregnancy rates of primiparous but not multiparous lactating dairy cows submitted to an Ovsynch program. Because cows were inseminated during summer, heat stress might have affected embryonic survival but the study was not designed to specifically address such an effect.
Experiments were performed to examine the growth-promoting effects of recombinant bovine growth hormone (rbGH) in the euryhaline tilapia (Oreochromis mossambicus). A radioreceptor assay using a crude membrane preparation of tilapia liver revealed that rbGH was about 100-fold less potent than native tilapia GH (tGH) in displacing 125I-labeled tGH. Bovine prolactin (bPRL) was equipotent to bovine GH indicating that the GH receptor of tilapia does not distinguish mammalian GH from mammalian PRL. When juvenile tilapia, weighing 1 g, were maintained at 28 °C and received intraperitoneal injection of rbGH at doses of 0.1, 1 or 10 μg/g weekly for 8 weeks, no significant effect on growth was observed. A second experiment examined weekly doses ranging from 1 to 50 μg/g for 16 weeks, using 1 g fish maintained at 23 °C. rbGH (50 μg/g) significantly increased growth after 14 and 16 weeks, although the growth rate was significantly less than those held at 28 °C. More pronounced growth-promoting effects were observed, however, when fish weighing 5 g and held at 29 °C were injected with rbGH at doses of 100 and 1000 μg/g once a week for 4 weeks. A single injection of a sustained-release formulation of rbGH (Posilac®, 100 and 1000 μg/g) also elicited growth-promoting effects in fish weighing 4 g and kept at 29 °C. Treatment with rbGH, Posilac® or bovine serum albumin (BSA) elicited significant increases in plasma levels of immunoglobulin (IgM) in a dose-dependent manner. By contrast, there was no change in plasma levels of lysozyme activity in rbGH- or Posilac®-injected fish compared with controls. An uptake and clearance study confirmed a slower decline in circulating levels of rbGH following Posilac® injection compared with rbGH in saline. There was no change in plasma concentration of tGH after rbGH treatment, indicating that GH secretion from the tilapia pituitary was unaffected by high plasma levels of rbGH. The relative refractoriness of juvenile tilapia to growth-promoting effects of rbGH compared with that of other species may be due to the specific nature of the tGH receptor in recognizing the homologous hormone.
Tilapia (n=12 per treatment in duplicate) were subjected to two different dietary levels of lipid (∼8% and 17%) and injected doses of recombinant bovine growth hormone (2.5 and 5.0 μg rbGH g−1 body weight week−1). The effects of these treatments were examined with respect to their impact upon growth and body shape. Tilapia fed high-lipid diets expressed increased weight and length gains (P<0.05). Accelerated growth in body weight and length was recorded in both dietary groups with injection of the lower dose of GH (P<0.05). However, no effect was seen in fish given the higher GH dose. Limited interactions between GH and dietary lipid were recorded during the experiment and feed efficiencies were similar for all groups. High dietary lipid increased body lipid levels (P<0.01). Gender differences, favouring females (P<0.01) for gonadosomatic and males (P<0.01) for intestinal indices, were recorded, but GH and diet were without overall effect. However, higher dietary lipid increased hepatosomatic indices (P<0.05). Multivariate tests of significance of whole body outline demonstrated highly significant (P<0.01) differences between treatment groups, with GH injection increasing post-orbital length. Head shape was profoundly impacted (P<0.01) by GH, which caused a visual broadening and shortening following examination by superimposition. Analysis of the syncranium using X-radiography illustrated no differences between groups suggesting that external shape change resulted due to modifications to animal physique.
The effect of treating rainbow trout (initial weight=51 g, T=10–11.5°C, fed to satiation), with recombinant bovine placental lactogen (PL, 2 μg g−1 body weight week−1) or growth hormone (GH, 2 μg g−1 body weight week−1), upon growth, feed conversion, sensory characteristics and fillet composition was investigated, with reference to three control groups. Hormone treatments were given for a period of 5–6 weeks, followed by a period of 13 weeks during which animals were left undisturbed. Differences in proximate composition of carcass (P<0.0005) and entrails (P<0.01), but not skeleton, were observed when sampled fish (PL at 5 weeks, GH at 6 weeks, and control at 7 weeks) of similar length were compared. At trial termination, eight animals from each group were randomly caught and slaughtered. The left fillet of each fish was skinned, vacuum-packed and boiled for 5 min, while the right fillet was used for compositional analyses. A trained sensory panel for flavour, odour, texture and appearance examined boiled fillets. PL-treated fish were deemed to express superior characteristics to control or GH-treated trout, particularly for juiciness (P<0.05). GH-treated animals received lower scores (P<0.05) for both sweet odour and flavour. Concurrent with a higher score for dryness, GH-treated fish returned higher fillet protein content (P<0.05) than other groups.
The health of dairy cows given bovine somatotropin (bST) for one lactation was evaluated in 28 commercial herds located in four regions of the United States. At least six herds were in a region and at least one herd/region contained fewer than 60 cows. Cows (n = 1213) were assigned randomly to control or bST groups and were treated beginning in wk 9 to 10 of lactation and every 14 d until dry-off or d 400 of lactation. Management was according to site practices. Cows were observed for health-related signs by farm personnel daily and by the herd veterinarian biweekly. Average 305-d test-day milk yields were 932 kg greater for bST-treated cows. Pregnancy rates, days open, twinning, cystic ovaries, or abortions were unaffected by treatments. Supplementation of cows with bST had no effect on total mastitis cases, total days of mastitis, duration of mastitis, or the odds ratio of a cow to develop mastitis. Cows supplemented with bST used more medications for health events other than mastitis. This usage was associated primarily with treatments for disorders of the foot and hock. Supplemented cows had a slight increase in foot disorders. There was no effect of supplementation with bST on culling from the herd or removal from study. Overall, the results confirm that label directions for bST are adequate for safe use under field conditions. All clinical signs observed in this study occur normally in dairy herds and were managed in cows supplemented with bST.
We have previously reported growth-promoting effects of recombinant bovine growth hormone (rbGH) in Mozambique tilapia, Oreochromis mossambicus, after 4 weekly injections or a single injection of slow-releasing formulation (Posilac®) (Leedom et al. 2002). In order to obtain further understanding of the role of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis in growth in the tilapia, the effects of rbGH on plasma and mRNA levels of IGF-I were examined. Plasma IGF-I levels were significantly increased after rbGH and Posilac® injections, and a significant correlation was observed between plasma IGF-I levels, body length and mass in both treatments. IGF-I mRNA levels in the liver and in the skeletal muscle were also significantly increased after rbGH and Posilac® injections, indicating that IGF-I gene expression in these tissues is under control of circulating GH. IGF-I mRNA levels in the gill were not affected by treatment. Liver IGF-I mRNA levels were significantly correlated with body length and with body mass after rbGH and Posilac® injections. These results indicate that the growth-promoting effect of rbGH in this species is mediated to a significant extent via its stimulation of hepatic production of IGF-I and the resulting increase in plasma IGF-I, and also possibly through locally produced IGF-I in the skeletal muscle, acting in a paracrine or autocrine fashion.
Studies have shown that bovine placental lactogen (bPL) has partial somatogenic activity in vivo even though binding results clearly indicate bPL does not cause homodimerization of the bovine somatotropin receptor (bST-R). To help understand the receptor binding versus biological activity of bovine somatotropin (bST) and bPL we have developed a homologous model system. Full length bST-R was stably transfected into a murine lymphoid cell line, Ba/F3 and a hamster kidney cell line, BHK. From both transfected cell lines, clones were isolated (Ba/F3-C1 and BHK-24) which demonstrated specific binding of bST and, or bPL. Bovine ST stimulated proliferation of the Ba/F3-C1 clonal line over a dose range of 10 to 3000 pM with an EC50 of 100 pM. A bST variant (des 1-4 bST) and porcine ST (pST) which both have approximately 10% of the binding affinity for bST-R as native bST were 1 and 10% as potent as bST in this bioassay, respectively. This suggests that affinity and biological activity are correlated for this system. Proliferation was initiated through the bST-R because addition of a monoclonal antibody which recognizes the extracellular domain of bST-R and inhibits binding of bST to its receptor, inhibited bST-stimulated mitosis. However, even though the affinity of bPL for the bST-R is similar to that of bST, bPL antagonized the proliferative action of bST with an IC50 of 1 nM. Components of the somatogenic signal transduction pathway were also evaluated in both cell lines. Addition of bST to the cell cultures increased phosphorylation of JAK2 in Ba/F3-C1 and BHK-24 cells in a dose-responsive manner but bPL failed to increase phosphorylation of JAK2 in either cell line. In summary, these data support the hypothesis that ST-R homodimerization is necessary for bioactivity in this model system but fail to explain apparent somatogenic activity of bPL in vivo.
The effect of recombinant bovine somatotropin (bST) on the chemiluminescence, diapedesis, and expression of adhesion receptors (CD11a, CD11b, CD18) of isolated polymorphonuclear leukocytes was studied. The plasma concentrations of insulin-like growth factor-I (IGF-I), bST, cortisol, and alpha-lactalbumin were also monitored. In addition, general and local clinical symptoms and the differentiation of circulating leukocytes were also studied during experimentally induced Streptococcus uberis mastitis in cows. Ten cows were infected with 500 cfu of S. uberis O140J in both left quarters. Five cows were subcutaneously treated with 500 mg of recombinant bST 7 d before and after infection, and 5 control cows received the excipient. General (fever, tachycardia, inappetance, and depression) and local symptoms (swelling, pain, firmness, and flecks in milk) were more acute, severe, and longer-lasting in control cows. Treatment with bST had no effect on chemiluminescence and diapedesis of circulating polymorphonuclear leukocytes and no effect on the expression of adhesion receptors. Recombinant bST induced significantly higher IGF-I and bST concentrations in plasma. The leukopenia observed after infection was less pronounced in the bST-treated cows, and the number of circulating band neutrophils and metamyelocytes was significantly lower in the treated group. The concentration of cortisol did not differ between both groups, but the blood concentration of alpha-lactalbumin significantly increased in both groups from 6 d after infection. These results showed that treatment with recombinant bST improves animal welfare by protecting the cows from severe local and general clinical symptoms during subsequent S. uberis mastitis, but that it has no effect on chemiluminescence, diapedesis, and the expression of adhesion receptors of circulating polymorphonuclear leukocytes.
The primary objective of this study was to determine whether bovine placental lactogen stimulated additional mammary growth as assessed by milk yield from a lactation induced by steroids. Pubertal, nonpregnant Holstein heifers (n = 23) were given daily subcutaneous injections of estradiol-17 beta (0.05 mg/kg) and progesterone (0.25 mg/kg) for 7 d to initiate mammary growth. Prolactin secretion was suppressed in all heifers via bromocriptine, which was administered until d 15. Heifers were treated with either placental lactogen (40 mg/d; n = 12) or water (control group; n = 11) for 18 d. Lactation was induced by daily injection of dexamethasone for 3 d and twice daily injections of recombinant bovine prolactin for 5 d starting on d 18. From 3 to 8 wk of lactation, milk yield of heifers treated with placental lactogen was numerically higher (22%) than the yield of control heifers, but the difference was not significant because of the high coefficient of variation. Daily injection of bovine somatotropin (d 57 to 66 of lactation) increased milk yield of both groups and stimulated a greater numerical increase in milk yield for heifers that were treated with placental lactogen. These results support the hypothesis that bovine placental lactogen is mammogenic and is one of the factors that regulates mammary growth during pregnancy.
Size-selected (167±11 mm) female rainbow trout were: given a high (1·8 μg g−1body weight per week) or low (0·35 μg g−1) dose of recombinant bovine growth hormone (GH), delivered by cholesterol pellet implant; injected with a commercial bivalent (vibriosis–furunculosis) vaccine; provided with each dose of GH plus vaccine; implanted with a pellet alone; or left untreated (N=20 per group). Growth in each treatment group was monitored over a 7 week period. Four weeks into the trial, and at trial termination, head kidney neutrophils were quantified using a histochemical method, and their respiratory burst (CL) response evaluated (N=10 per group). By week 4 of the trial, high dose GH treatment was observed to enhance the CL response of vaccinated fish (P<0·05) above that of control and other groups. High dose GH treated animals also returned greater, although relative to week 4 data significantly lower, CL response at trial termination. Vaccination had an overall negative effect (P<0·05) upon trout growth performance during the trial, although this consequence was annulled when vaccine was co-administered with high dose GH. When considered conjointly with the findings of others, the results of the present investigation provide evidence in support of the existence of a hypothalamo-pituitary-immune axis in teleosts.
Experiments were undertaken to evaluate a sustained release recombinant bovine growth hormone (rbGH) formulation (Posilac®) in salmon. The investigation was divided into two parts. The first series of studies was used to establish optimal dosages and clearance rates for the exogenous protein in size-selected coho salmon, and to examine the effect of rbGH treatment upon smoltification. The second series of studies attempted to mimic the production setting, where chinook salmon were randomly selected from a stock of animals, and taken through smoltification to grow-out. In the first experiment, coho salmon were provided with a single injection of one of three doses (420, 1260, 4200 μg/g body weight equivalent) of the rbGH preparation (n ≥30/group), or were injected with a saline solution containing the high dose equivalent of rbGH. Controls were treated with BSA, given one of three (10, 30 or 100 μl) placebo carrier preparations without rbGH, or left untreated. Animals receiving rbGH by sustained-release expressed highly significant (P < 0.01) growth acceleration over a 20-week period of observation, when compared with the five control treatments. There were no significant differences in growth between the five control treatments. At the termination of the trial, control animals had doubled their weight and were 25% longer than starting values. In contrast, salmon receiving rbGH via sustained release were 5–7.5 times their starting weight and exhibited a 60–100% increase in length. Coho salmon injected once with the saline solution of rbGH grew significantly (P < 0.05) larger than control groups over the first 16 weeks of observation. However, at trial termination, control and saline rbGH animals were not statistically different in weight and length. Following the growth trial, fish were subjected to a 24-h seawater challenge. Plasma samples collected prior to and following challenge, indicated that rbGH-treated fish were better able to adapt to the hypersaline environment, as indicated by their increased ability to regulate plasma sodium (P < 0.05). Plasma profiles for rbGH determined that the protein was released from the Posilac® preparation for ≥ 20 weeks following injection. In the second experimental series, chinook salmon were provided with the high dose Posilac ® formulation (equivalent to approximately 6600 μg rbGH/g body weight), whereas controls received the placebo carrier alone (n = 856 for each group). The growth response was followed through transfer to sea water, and beyond for a period of 32 weeks. Significant differences (P < 0.01) between group weights and lengths were first observed following 12 weeks of observation, and maintained until trial end. Examination of size frequency distribution illustrated a significant (P < 0.05) broadening of the curves for rbGH-treated fish from week 8 onwards, indicating an overall increase in size variation.
Prolactin, a member of the somatotropin-prolactin-placental lactogen gene family, increases feed intake and rate of weight gain in several species. To determine whether prolactin affects growth performance and carcass composition in swine, recombinant porcine prolactin (rpPRL) was administered to finishing hogs. Doses of 0, 2, 4, 8, and 16 mg of rpPRL/d and 4 mg of recombinant porcine somatotropin (rpST)/d were administered to groups of seven barrows and seven gilts initially weighing 75.0 +/- .2 kg for a 28-d period. Recombinant pPRL did not alter feed intake or growth rate or affect carcass composition. In addition, most growth-related blood variables did not change, although plasma IGF-I was increased in the 8 and 16 mg of rpPRL treatment groups. At slaughter, mammary development was apparent in rpPRL-treated gilts and was characterized by distended alveolar and ductal lumina and presence of secretory material. In rPST-treated hogs, feed intake was decreased 28% (P < .01), gain/feed was increased more in barrows than in gilts (59 vs 39%, treatment x sex interaction, P = .035), and growth rate was increased 22%, but in barrows only (treatment x sex interaction P = .005). Compared with those in control hogs, circulating concentrations of IGF-I, insulin, and glucose were 175, 311, and 22% higher, respectively, and of blood urea nitrogen were 62% lower in rpST-treated hogs (P < .05). These results suggest that rpPRL, at the doses administered, does not increase feed intake in finishing hogs in contrast to rats and other species.
The effect of recombinant bovine placenta) lactogen (rbPL) treatment upon growth of juvenile chinook salmon, Oncorhynchus tshawytscha (Walbaum) (14.0 ± 0.31 g wet wt), was examined over a period of 6 weeks. Experimental animals were either injected (5 μg rbPL g−1 week−1), implanted with a cholesterol pellet containing 0.4 mg rbPL (approximately 4 μg g−1 week−1), or orally and rectally intubated with 7.5 μg rbPL g−1 week−1. Control animals were injected with bovine serum albumen (BSA), 5 μg g−1 week−1, implanted with a placebo or orally intubated (7.5 μg BSA g−1 week−1). Significant (P < 0.05) growth acceleration was recorded for rbPL-injected and pellet-implanted groups from week 2 onwards when compared against all other groups. Oral or rectal intubation of rbPL (7.5 μg rbPL g−1 week−1), however, was without effect. Condition factor decreased in all groups, but was significantly lower in rbPL-injected and pellet-implanted fish at trial end when compared against controls. No differences were recorded between groups for per cent body moisture or relative gut length. Hepatosomatic index was significantly (P < 0.05) higher in rbPL-injected and rbPL-implanted chinook salmon versus other fish.
The acute regulation of lipolysis in the adipose tissue of ruminants was evaluated with lactating cows (n = 4) and growing ewe lambs (n = 11). Subcutaneous adipose tissue was obtained by biopsy or at slaughter and was incubated with varying concentrations of biologically active insulin-like growth factors-I and -II (IGF-I, IGF-II), somatotropin (ST), prolactin (PRL), or placental lactogen (PL) to determine the effect of these hormones on lipolysis. Complimentary studies were conducted to examine the effects of IGF-I and IGF-II on the acute regulation of lipolysis in adipose tissue from lactating ewes and wethers under a variety of incubation conditions. Isoproterenol (ISO), a beta-adrenergic agonist known to rapidly stimulate lipolysis, was used as a positive control. Incubation with ISO for 3 hr resulted in a significant increase in the rates of lipolysis. However, there was no stimulation of lipolysis over the 3-hr incubation at any concentration or under any conditions for IGF-I or IGF-II. Furthermore, ST, PRL, or PL had no acute effects on the rates of lipolysis in adipose tissue. These data demonstrate that IGF-I, IGF-II, ST, PRL, and PL are not acute effectors of the lipolytic rate in the adipose tissue of ruminants.