Long-term feed intake regulation in sheep is mediated by opioid receptors.

These experiments were conducted to determine if 1) syndyphalin-33 (SD33), a mu-opioid receptor ligand, affects feed intake; 2) SD33 effects on feed intake are mediated by actions on opioid receptors; and 3) its activity can counteract the reduction in feed intake associated with administration of bacterial endotoxin. In Exp. 1, 5 mixed-breed, castrate male sheep were housed indoors in individual pens. Animals had ad libitum access to water and concentrate feed. Saline (SAL; 0.9% NaCl) or SD33 (0.05 or 0.1 micromol/kg of BW) was injected i.v., and feed intake was determined at 2, 4, 6, 8, 24, and 48 h after the i.v. injections. Both doses of SD33 increased (at least P < 0.01) feed intake at 48 h relative to saline. In Exp. 2, SAL + SAL, SAL + SD33 (0.1 micromol/kg of BW), naloxone (NAL; 1 mg/kg of BW) + SAL, and NAL + SD33 were injected i.v. Food intake was determined as in Exp. 1. The SAL + SD33 treatment increased (P = 0.022) feed intake at 48 h relative to SAL + SAL. The NAL + SAL treatment reduced (at least P < 0.01) feed intake at 4, 6, 8, 24, and 48 h, whereas the combination of NAL and SD33 did not reduce feed intake at 24 (P = 0.969) or 48 h (P = 0.076) relative to the saline-treated sheep. In Exp. 3, sheep received 1 of 4 treatments: SAL + SAL, SAL + 0.1 micromol of SD33/kg of BW, 0.1 microg of lipopolysaccharide (LPS)/kg of BW + SAL, or LPS + SD33, and feed intake was monitored as in Exp. 1. Lipopolysaccharide suppressed cumulative feed intake for 48 h (P < 0.01) relative to saline control, but SD33 failed to reverse the reduction in feed intake during this period. These data indicate that SD33 increases feed intake in sheep after i.v. injection, and its effects are mediated via opioid receptors. However, the LPS-induced suppression in feed intake cannot be overcome by the opioid receptor ligand, SD33.

Lysine requirement of finishing pigs administered porcine somatotropin by sustained-release implant.

To alleviate the need for daily injection of porcine somatotropin (pST), a sustained-release implant (pSTSR) was devised that continuously delivers a daily dose of 2 mg of pST for 42 d. Ninety-six white composite (Large White x Landrace) finishing barrows (83.6 +/- 1.2 kg BW) were assigned to receive zero or two pSTSR implants (4 mg pST/d) and to consume one of six diets differing in total Lys concentration (0.29, 0.52, 0.75, 0.98, 1.21, or 1.44%, as-fed basis). Diets were formulated to be isocaloric and based on the ideal protein concept. Pigs were housed individually, allowed ad libitum access to feed and water, and slaughtered at 112 kg of BW. The pSTSR affected neither ADG (P = 0.88) nor 10th rib LM area (LMA; P = 0.51), but it decreased (P < 0.01) ADFI, average backfat thickness, 10th rib fat depth, weights of leaf fat and ham fat, improved (P < 0.05) G:F, and increased (P < 0.01) weights of four trimmed lean cuts (T-cuts), and percentages of ham lean and bone. Increasing total Lys increased ADG (quadratic; P < 0.05) and ADFI (linear; P < 0.01). The G:F, plasma urea N concentrations (PUN), and T-cuts were affected by the interaction pSTSR x dietary Lys (P < 0.01). Without pSTSR, the G:F did not differ (P = 0.37) among pigs fed 0.52% and greater total Lys. With pSTSR, the G:F was less (P < 0.05) for pigs fed 0.52% than 0.98 and 1.44% total Lys. Increases in dietary total Lys resulted in increased PUN (P < 0.01), and incremental increases were less in pSTSR-implanted pigs. Maximal yield of T-cuts was at 0.98% dietary total Lys in nonimplanted pigs and 1.21% total Lys in pSTSR-implanted pigs. Estimates of total Lys requirements of pigs without and with pSTSR, respectively, were 0.52 and 0.86% for growth (ADG and G:F) and 0.73 and 0.88% for lean production (LMA and T-cuts). Equivalent apparent ileal digestible Lys requirements of pigs without and with pSTSR, respectively, were 0.44 and 0.68% for growth, and 0.62 and 0.75% for lean production. With ADFI of 3.5 kg daily, an intake of approximately 26.1 g of total daily Lys (0.75%) or 22.4 g of apparent ileal digestible Lys is needed to maximize lean production in finishing barrows receiving 4 mg pST/d via sustained-release implant.

Intracerebroventricular melanin-concentrating hormone stimulates food intake in sheep.

Melanin-concentrating hormone (MCH) stimulates feeding when injected intracerebroventricularly (ICV) in rats. At present it is not clear whether the function of MCH is similar in ruminants, which are species with a continuous delivery of nutrients. Therefore the current investigation sought to determine the role of MCH in sheep. In the first experiment, six, castrate male sheep were satiated and received one of four treatments [saline, 0.1, or 1.0 nmol/kg MCH, and NPY (0.1 nmol/kg)] injected ICV over 30s, then infused ICV for 6 h ( approximately 500 microl/h). Food intake was measured for 2 h before and at 2, 4, 6, 8, 12 and 24 h. In this experiment, feed intake was increased (P

Alterations in the growth hormone/insulin-like growth factor I pathways in feline GM1 gangliosidosis.

Cats affected with feline GM1 gangliosidosis, an autosomal, recessively inherited, lysosomal enzymopathy, have progressive neurological dysfunction, premature thymic involution, stunted growth, and premature death. Although increased membrane GM1 gangliosides can result in increased apoptosis of thymocytes, there is not a direct correlation between thymocyte surface GM1 and thymic apoptosis in vivo, suggesting that other factors may be important to the pathogenesis of thymic involution in affected cats. Because GH and insulin-like growth factor I (IGF-I) are important hormonal peptides supporting thymic function and affecting growth throughout the body, particularly in the prepubescent period, several components of the GH/IGF-I pathway were compared in GM1 mutant and normal age-matched cats. GM1 mutant cat serum IGF-I concentrations were reduced significantly compared with those in normal cats by 150 days of age, and GM1 mutant cats had no peripubertal increase in serum IGF-I. Additionally, IGF-binding protein-3 was reduced, and IGF-binding protein-2 was elevated significantly in GM1 mutant cats more than 200 days of age. Liver IGF-I messenger RNA and pituitary GH messenger RNA both were reduced significantly in GM1 mutant cats. After stimulation by exogenous recombinant canine GH, serum IGF-I levels increased significantly in GM1 mutant cats, indicating that GH/IGF-I signaling pathways within the liver remain intact and suggesting that alterations are external to the liver.

Interactions between environmental temperature and porcine growth hormone (pGH) treatment in neonatal pigs.

Age-dependent interactions between environmental temperature and porcine growth hormone (pGH) treatment on the function of the somatotrophic axis were evaluated in the neonatal pig. At 3 d of age, 40 Landrace x Yorkshire x Duroc piglets received intraperitoneal implants containing either recombinant pGH (0.5 mg/d; n = 20) or vehicle (control; n = 20). Piglets were maintained at either a low (21 degrees C, 50% relative humidity; n = 20) or high (32 degrees C, 50% relative humidity; n = 20) temperature. At 4 and 6 wk of age, 5 pGH-treated and 5 control piglets from each thermal group were sacrificed for tissue collection. Blood samples were collected at the time of sacrifice and analyzed for serum concentrations of GH, insulin-like growth factor 1 (IGF-1), and IGF-2. Liver RNA was analyzed for mRNAs specific for the GH receptor, IGF-1, IGF-2, and IGF binding protein 3. There was no effect of pGH treatment (P = 0.4) on average daily gain; however, both age (P = 0.002) and temperature (P = 0.001) had an effect on average daily gain such that those animals maintained at a low temperature and those sacrificed at 6 wk had greater average daily gains. Serum concentration of GH was elevated (P = 0.003) by pGH treatment and was lowest in the 6-wk-old group (P = 0.008). Serum concentration of IGF-1 was elevated (P = 0.007) by pGH treatment and increased with age (P = 0.01). Liver GH receptor mRNA was unaffected (P > 0.5) by pGH treatment, but was greater in the 6-wk-old group (P < 0.0001) and in piglets maintained at the high temperature (P = 0.04). IGF-1 mRNA was enhanced by pGH treatment (P = 0.0003) and by exposure to the high temperature (P = 0.04), but did not differ (P > 0.5) between age groups. IGF-2 mRNA was greater (P = 0.0009) in the 4-wk-old group and in piglets maintained at the high temperature (P = 0.007), but was unaffected (P = 0.5) by pGH treatment. IGF binding protein 3 mRNA increased with age (P = 0.0004) and was stimulated by pGH treatment in the 6-wk-old group (P = 0.034). The relatively lower level of GH receptor and IGF mRNAs in conjunction with greater growth in the cold environment suggests that somatotrophic gene expression in the liver is not rate limiting for growth in the neonatal pig.

Growth, body composition, and endocrine responses to chronic administration of insulin-like growth factor I and(or) porcine growth hormone in pigs.

The actions of IGF-I, alone and in combination with porcine growth hormone (pGH), on growth and circulating endocrines and metabolites important in growth were investigated in peripubertal-age Meishan barrows. Pigs were assigned to four treatments: control, buffer; IGF-I, 33 microg rhIGF-I/kg BW injected twice daily; pGH, 33 microg rpGH/kg BW injected once daily; and IGF-I+pGH, 33 microg rhIGF-I/kg BW injected twice daily plus 33 microg rpGH/kg BW injected once daily. Treatments were administered for 28 d. Feed intake, BW, and backfat were recorded and blood samples were collected weekly. At slaughter, organ and primal cut weights were recorded. Offal and half the carcass were ground for chemical analysis. Serum concentrations of IGF-I on d 7, 14, 21, and 28 in the IGF-I, pGH, and IGF-I+pGH groups were increased 60, 107, and 131%, respectively, compared with those of the control group. Administration of pGH increased gain 43%, feed efficiency 60%, carcass protein accretion 88%, and trimmed lean cuts 16%, whereas IGF-I administration increased gain 22%, carcass protein accretion 33%, and trimmed lean cuts 5%. There was little difference in responses to administration of IGF-I+pGH and pGH alone except that coadministration of IGF-I with pGH reduced the ability of pGH to suppress backfat gain (P < .02). Even though administration of IGF-I resulted in a 60% increase in chronic nadir serum concentrations of IGF-I, only a few growth and carcass measures were changed when compared with control pigs. These included increased (P < .05) weight of body, leaf fat, kidneys, and belly. The actions of pGH on growth of pigs were not mimicked, and some were countermanded by administration of IGF-I at a dose that produces significantly increased serum concentrations of IGF-I.

Radiographic, densitometric, and biomechanical effects of recombinant canine somatotropin in an unstable ostectomy gap model of bone healing in dogs.

OBJECTIVE: To determine the effect of recombinant canine somatotropin (STH) on radiographic, densitometric, and biomechanical aspects of bone healing using an unstable ostectomy gap model. STUDY DESIGN: After an ostectomy of the midshaft radius, bone healing was evaluated over an 8-week period in control dogs (n = 4) and dogs receiving recombinant canine STH (n = 4). ANIMALS OR SAMPLE POPULATION: Eight sexually intact female Beagle dogs, 4 to 5 years old. METHODS: Bone healing was evaluated by qualitative and quantitative evaluation of serial radiographs every 2 weeks. Terminal dual-energy x-ray absorptiometry and three-point bending biomechanical testing were also performed. RESULTS: Dogs receiving STH had more advanced radiographic healing of ostectomy sites. Bone area, bone mineral content, and bone density were two to five times greater at the ostectomy sites of treated dogs. Ultimate load at failure and stiffness were three and five times greater in dogs receiving STH. CONCLUSIONS: Using the ostectomy gap model, recombinant canine STH enhanced the radiographic, densitometric, and biomechanical aspects of bone healing in dogs. CLINICAL RELEVANCE: Dogs at risk for delayed healing of fractures may benefit from treatment with recombinant canine STH.

The effects of dietary restriction on insulin-like growth factor (IGF)-I and II, and IGF-binding proteins in chickens.

The effect of feed (energy/protein) restriction on circulating concentrations of insulin-like growth factor (IGF)-I and II, and IGF-binding proteins (IGFBPs) was examined in young (4-week-old) chickens. Increasing levels of feed restriction caused progressive growth retardation, as evidenced by decreased body-weight gain and reduced bone growth. Plasma concentrations of both IGF-I and IGF-II were decreased, and the degree of reduction in the plasma concentrations of these growth factors appeared to be related to the magnitude of feed restriction. A tendency for greater decreases in these growth factors appeared to be associated with greater feed restriction at the majority of time points evaluated. However, nutritional restriction had a greater effect on plasma concentrations of IGF-I than on those of IGF-II. The reductions in plasma concentrations of IGF-I were observed earlier in the experiment and at a lower degree of nutritional deprivation than for plasma concentrations of IGF-II, possibly suggesting greater sensitivity of IGF-I plasma concentrations to feed restriction. Three IGFBPs with molecular weights of 30, 36, and 40 kDa were detected by radioligand assay following separation by SDS-electrophoresis. The 30-kDa IGFBP was most affected by feed restriction with binding activity of this IGFBP increased by 2 days of feed restriction irrespective of the degree of feed deprivation. The binding activity of the 36-kDa IGFBP was increased, albeit transiently, on the second day of feed restriction. Nutritional restriction had no discernible effect on the binding activity of the 40-kDa IGFBP. Increases in the binding activity of the 30-kDa IGFBP appeared to correspond with the observed decreases in IGF-I plasma concentrations. This suggests decreased bioavailability of IGF-I, and possibly IGF-II, attributed to the formation of a complex between IGF-I and the 30-kDa IGFBP during feed restriction. The initial increase in binding activity of the 36-kDa IGFBP may suggest that this binding protein also plays a role in the regulation and availability of circulating concentrations of IGF-I and IGF-II. Although the binding activity of the 40-kDa IGFBP was unaffected by feed restriction, we can not exclude its importance in the regulation of IGF-I. The substantial binding activity of the 40-kDa IGFBP observed in this experiment suggests that it is one of the major chicken IGFBPs, and that its role in IGF-I regulation warrants further study.

Ontogeny of insulin-like growth factors (IGF-I and IGF-II) and IGF-binding proteins in the chicken following hatching.

The present study examined plasma concentrations of insulin-like growth factor (IGF)-I, IGF-II and IGF-binding proteins (IGFBPs) during posthatch growth and development in chickens. Three distinct proteins which bound 125I-IGF-I were observed irrespective of age or sex, these having apparent molecular weights of 22, 28, and 36 kDa. The major IGFBP present during much of the growth and development period was the 28-kDa form followed by the 36-kDa form. Plasma concentrations of IGF-II and of the 22-kDa IGFBP showed little ontogenic variation with the exception of elevated levels of the 22 kDa IGFBP in 1-day-old chicks. The circulating concentrations of IGF-I and of the 28-kDa IGFBP increased progressively between the time of hatching to reach a maximum at 6 weeks of age and subsequently declined to lower levels in adults. Somewhat similarly, the 36-kDa IGFBP increased during early pre- and posthatching growth to a maximum at 6 weeks of age. There were marked sex differences in circulating concentrations of IGF-I in young (4 week) and adult chickens and in the 36-kDa IGFBP in the adult, both being lower in females. Estrogen treatment of adult male chickens decreased the circulating concentrations of IGF-I together with the level of both the 28- and 36-kDa IGFBPs. Testosterone treatment had no effect on the circulating concentrations of either IGF-I or IGFBPs in adult female chickens. We conclude that the relative levels of IGF-I, IGF-II, and the IGFBPs change with age. In addition, circulating concentrations of estrogen may play a role in the regulation of IGF-I and IGFBPs.

Ontogenic changes in the circulating concentrations of insulin-like growth factor (IGF)-I, IGF-II, and IGF-binding proteins in the chicken embryo.

The ontogeny of circulating concentrations of insulin-like growth factor (IGF-)-I, IGF-II, and IGF-binding proteins (IGF-BPs) was examined in the chick embryo. Distinct ontogenic changes in the circulating concentrations of IGF-I and IGF-II were observed. The present study confirms the overall profile for circulating concentrations of IGF-I. During middevelopment, plasma concentrations of IGF-I increased to a maximum which was attained on Day 14.5 of incubation. Thereafter, plasma concentrations of IGF-I declined with decreases (P < 0.05) between Days 14.5 and 15.5 and between Days 16.5 and 17.5 of incubation. In contrast to the monophasic profile for IGF-I, plasma concentrations of IGF-II were maximal on Day 10.5 of incubation and declined to a nadir on Day 17.5 of incubation. In late developmental stages (17.5 or 18.5 days of incubation), three IGF-BPs, having molecular weights of 22, 28, and 36 kDa, were detected in the plasma of chick embryos. No significant ontogenic changes in the circulating levels of the 28- and 36-kDa IGF-BPs were observed. However, it should be noted that prior to Day 17.5 of incubation, the 22-kDa IGF-BP was nondetectable in the circulation. The role of these changes in the functioning of IGF in embryonic development is discussed.

Growth performance, endocrine, and metabolite responses of finishing hogs to porcine prolactin.

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.

Suppression of somatotroph function induced by growth hormone treatment in neonatal pigs.

The effect of recombinant porcine growth hormone (pGH) treatment on pituitary function was evaluated in young pigs. Piglets received intraperitoneal recombinant pGH implants (0.5 mg/d sustained release) or vehicle implants beginning at 3 d of age. Ten piglets were sacrificed at 4 and 6 wk of age (five piglets/treatment group) for the collection of pituitary glands, blood, and liver tissue. Blood samples also were drawn at 3 and 12 d of age. Serum concentrations of GH, prolactin (PRL), thyroid-stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1) and IGF-2 were evaluated. Levels of IGF-1 and IGF-2 mRNA were determined in liver samples. Treatment with GH increased circulating levels of GH and IGF-1 (P < 0.01), but not PRL, TSH, or IGF-2. Hepatic IGF-1, but not IGF-2, mRNA levels were increased by pGH (P < 0.001). Cultured pituitary cells from each animal were challenged with 0.1, 1, and 10 nM GH-releasing hormone (GHRH); 2 nM 8-Br-cAMP; or 100 nM phorbol myristate acetate. The release of GH from cultured pituitary cells was stimulated by all secretagogues (P < 0.001). The secretion of GH, but not PRL or TSH, in culture was inhibited by previous in vivo GH treatment (P < 0.001). Similarly, cellular GH, but not PRL or TSH, content was lower in the GH-implant group (P = 0.005). Cell cultures from 6-wk-old piglets secreted more GH, but not PRL or TSH, than cultures from 4-wk-old piglets (P < 0.05). Likewise, cellular GH, but not PRL or TSH, content was greatest in cultures from 6-wk-old animals (P = 0.002). Piglet growth was not affected by exogenous GH treatment (P = 0.67). These results demonstrate that exogenous pGH treatment selectively down-regulates somatotroph function in young pigs.

Thymic, gonadal, and endocrine relationships in gilts and boars administered porcine somatotropin.

We hypothesized that much of the positive effect of porcine somatotropin (pST) on the immune system would be offset by the pST/IGF stimulation of gonadal function and that there would be negative effects on thymic weight and function from increased androgens in males. Male and female hogs (78 boars, 90 gilts) representing three genetic lines (lean, obese, and crossbred meat type) received 0, 2, or 4 mg of recombinant pST/d via implant for 42 d. Blood samples were collected on 0, 7, 14, 28, and 42 d of the trial for changes in pST, IGF-I, IGF-II, thymosin beta 4, dehydroepiandrosterone/dehydroepiandrosterone sulfate (DHEA/DHEASO4), and testosterone concentrations. Thymic, splenic, gonadal, and adrenal weights were collected at slaughter (d 42). Thymic weights increased with dose of pST in both sexes (P < .01), but splenic weights were unaltered. Adrenal weights increased with dose of pST (P < .01), but gonadal weights showed no response to pST in either sex or any line. Overall, concentrations of pST, IGF, and thymosin beta 4 increased with dose of pST. Serum testosterone concentrations in boars declined with dose of pST in lean and obese lines, and DHEA/ DHEASO4 declined in all lines with pST treatment. Testicular testosterone concentrations were not different among lines or doses of pST, indicating no stimulatory effect of increased pST/IGF-I on Leydig cell function. Although pST and its effects through increased circulating IGF are thought to be overall stimulants of growth and protein accretion, the actions on the tissues of the immune system (thymus/spleen) and steroidogenic tissues (adrenal/gonadal) can be selective. Increases in thymic weights and thymosin beta 4 concentrations from pST treatment in boars were partially due to the pST-induced decline in circulatory androgens, and the responses found in this in vivo model do not support pST/IGF effects documented in in vitro systems on Leydig cell function.

Effects of porcine somatotropin on circulating testosterone concentrations in boars and mechanism of action.

Four experiments were conducted to elucidate the effects of porcine somatotropin (pST, growth hormone) on circulating testosterone concentrations in boars. In Exp. 1, jugular-cannulated obese boars were administered 4 mg recombinant (r) pST/d for 24 d before collection of samples at 15-min intervals over 6 h for measurement of pST, testosterone, and LH. Somatotropin treatment decreased plasma concentrations of testosterone and LH (P < .05). In Exp. 2, White composite boars were administered rpST with implants (4 mg/d) for 10 to 28, 16 to 28, or 22 to 28 wk of age. Reductions in testosterone concentrations were proportional to the length of time rpST was administered; boars treated for 18 wk had the lowest testosterone concentrations. Concentrations of LH declined throughout the study in rpST-implanted boars but remained static in untreated, control boars. In vitro production of testosterone and dehydroepiandrosterone/dehydroepiandrosterone sulfate was unaffected by rpST treatment, and hCG stimulation of in vitro androgen secretion was similar in rpST and control treatments. In Exp. 3, i.v. injection of pituitary pST (USDA-B1; 5 micrograms/kg BW) into jugular-cannulated White composite and Meishan boars resulted in an acute increase in circulating LH followed by an increase in testosterone concentrations, which then declined to below preinjection levels at 6 to 7 h after pST injection. Multiple injections, two or four per day, of 5 micrograms pST/kg BW resulted in decreased testosterone concentrations in White composite boars, whereas in Meishan boars testosterone concentrations were unaffected (Exp. 4). Concentrations of LH were not different from control values in either breed, but in both breeds, four injections of pST per day produced lower LH concentrations than did two injections per day (P < .01). Depression of circulating concentrations of androgens in boars requires extended periods of pST treatment.

Endocrine and metabolite responses to porcine growth hormone administered by sustained release implant for different lengths of time in male pigs.

The effects of long term administration of GH on serum concentrations of hormones and metabolites was investigated in intact and castrate male swine. At 10 weeks of age, male swine were assigned to six treatments (n = 10/group): nonimplanted intact and castrate males; intact males implanted for 6 weeks, from 22-28 weeks of age; intact males implanted for 12 weeks, from 16-28 weeks of age; and intact and castrate males implanted for 18 weeks, from 10-28 weeks of age. Recombinant porcine GH was administered with sustained release implants designed to deliver a dose of 4 mg/day for 6 weeks. Throughout the study, blood samples were collected, and serum was harvested to quantitate circulating concentrations of glucose, urea nitrogen, GH, insulin, insulin-like growth factor I (IGF-I), IGF-II, and PRL. The pattern of administered GH in the serum suggests that the presence of testes and prior treatment with GH influence GH clearance. Somatotropin treatment elevated serum concentrations of GH and increased serum levels of glucose, insulin, IGF-I, and IGF-II in both intact and castrate animals. However, during the prepubertal period of 10-16 weeks, GH-treated intact males were resistant to the diabetogenic actions of GH, whereas significantly increased serum levels of glucose and insulin occurred in GH-treated castrates during this period. Changes in serum levels of IGF-I throughout the study and in insulin after the first 6 weeks followed the pattern of circulating GH concentrations in the treated animals. Serum concentrations of IGF-II were increased after GH administration, but, in contrast to the IGF-I response, IGF-II levels remained elevated as GH concentrations waned in the latter portion of the implant period. The maintenance of higher serum levels of IGF-II may be less dependent upon GH than are insulin and IGF-I. Administration of GH to intact males is more efficacious in altering metabolites and hormones, with the exception of IGF-I, during the peripubertal and postpubertal periods than during the prepubertal period.

Metabolic and histologic effects of recombinant canine somatotropin on bone healing in dogs, using an unstable ostectomy gap model.

OBJECTIVE: To investigate the effect of recombinant canine somatotropin (STH) on the metabolic and histologic aspects of bone healing in dogs, using an unstable ostectomy gap model. ANIMALS: 8 mature dogs. PROCEDURE: A 3-mm ostectomy of the mid portion of the radius was performed in all dogs. Implants designed to release STH at a rate of 4 mg/d were placed SC in 4 dogs (treated group [STHG]), and another 4 dogs received no implants (control group [CG]). Serum concentrations of STH, insulin-like growth factor I, and osteocalcin were determined before surgery, and weekly for 8 weeks. Scintigraphic evaluation of the ostectomy sites was performed before surgery, and at weeks 2, 4, 6, and 8 after surgery. Histologic evaluation ofthe ostectomy sites was performed at the conclusion of the study at week 8. RESULTS: Significant (P < 0.05) increases in serum STH, insulin-like growth factor I, and osteocalcin concentrations were observed in dogs of the STHG during the 8-week study period. Scintigraphic activity of the ostectomy sites was increased in dogs of both groups, but dogs of the STHG had significantly (P < 0.05) greater activity, compared with dogs of the CG. Coalescence of nuclear activity across the ostectomy site was observed in dogs of the STHG, whereas dogs of the CG maintained 2 distinct areas of metabolic activity. Histologically, dogs of the STHG had bridging calluses with areas of endochondral ossification and ongoing osteogenic activity, whereas dogs of the CG had nonossified fibrocartilage typical of nonunion fractures. CONCLUSION: Using the ostectomy gap model, recombinant canine STH enhanced the metabolic and histologic aspects of bone healing in dogs.

The effects of bovine somatotropin (bST) and porcine somatotropin (pST) on growth factor and metabolic variables in horses.

Effects of exogenous pST and bST on metabolic and growth factor variables were examined in three studies with lighthorse mares (455 to 545 kg). In Study 1, eight mares received five s.c. injections of bST or pST (30 mg/d). In Studies 2 and 3, five mares received one s.c. injection of a prolonged release formulation designed to deliver 500 mg of bST (Study 2) or pST (Study 3) over 14 d. Blood samples were collected for several days before injection to establish baseline values, at frequent intervals during treatment, and for several days thereafter. In all studies, blood urea nitrogen concentrations were decreased (P < .001) and insulin-like growth factor I (IGF-I) concentrations were increased (P < .001) within 48 h after bST or pST injection relative to pretreatment values. Similarly, insulin and glucose were increased (P < .001) relative to pretreatment values, after bST or pST administration. In Studies 2 and 3, circulating ST concentrations were increased (P < .001) for at least 14 d after injection, despite severe local tissue reactions at the prolonged release formulation injection site. Insulin-like growth factor I ligand blotting of serum revealed bands with molecular weights (MW) of 45, 32, 30, and 18 kDa, and two bands of > 96 kDa. These results indicate that 1) bST and pST are biologically active in horses, which respond metabolically to exogenous ST in a manner similar to other mammalian species, 2) circulating IGF binding proteins are present in horses, and 3) the commercially available dairy cow product POSILAC (Monsanto, St. Louis, MO) is not appropriate for the delivery of bST in horses due to injection site reactions accompanying the administration of the oil-based prolonged release formulation.

Growth performance, carcass characteristics, and sensory attributes of boars administered porcine somatotropin by sustained-release implant for different lengths of time.

We investigated the effect of sustained-release implant administration of porcine somatotropin (pST) (4 mg/d) to male pigs for different lengths of time before slaughter. Crossbred white boars were assigned to six groups (n = 10/ group); B0, non-implanted boars; B6, boars implanted from 22 to 28 wk of age; B12, boars implanted from 16 to 28 wk of age; B18, boars implanted from 10 to 28 wk of age;C0, non-implanted castrates; and C18, castrates implanted from 10 to 28 wk of age. Castration was at 65 d of age. All pigs were slaughtered at 28 wk of age, and measures of offal and carcass components were recorded. Loin chops were collected for sensory evaluation. During the trial the pigs were maintained in individual pens with ad libitum access to water and a 19% CP corn-soybean meal diet containing 1.08% calculated lysine. Although pST reduced feed intake in castrates (P < .01), the effect in boars was nonsignificant. Slaughter weight was increased in a linear (P < .04) manner with length of pST treatment of boars, and slaughter weights of castrates given pST were greater (P < .01) than those of control castrates. The product of the changes in feed intake and gain resulted in greater efficiency of gain in pST-treated pigs than in control pigs (P < .01). A linear effect (P < .06) of length of pST treatment on trimmed lean cut weights of boars was noted. The weights of trimmed lean cuts produced by castrates treated for 18 wk with pST and boars treated for 12 or 18 wk were similar. Boars given pST for 18 wk had improved (P < .10) boar taint scores compared with untreated boars. Boars and castrates given pST for 18 wk had a similar rates of gain and weights of trimmed lean cuts. Efficiencies of gain were greater in pST-treated boars and castrates than in untreated boars, which were superior to untreated castrates in efficiency of gain.

Administration of porcine somatotropin by daily injection: growth and endocrine responses in genetically lean and obese barrows and gilts.

Influences of genotype and sex on responses to porcine somatotropin (pST) administered by daily injection were examined in genetically lean and obese gilts and barrows. Pigs (59 +/- 1.4 kg BW, eight per pST dose x line x sex) were injected daily with pST at doses of 0, 2, and 4 mg/d for 6 wk. Administration of pST induced dose-dependent decreases in feed intake and rate of backfat deposition, whereas rate and efficiency of gain were increased in a quadratic manner indicating that 4 mg of pST/d approached the optimal dose. These live measures of growth were also influenced (P < .05) by sex and line. Line, sex, and pST dose effects (P < .05) were noted for most offal components and carcass components. Quantity of lean and bone in the ham was increased (P < .01) and that of fat decreased (P < .01) with dose of pST. Throughout the trial pST induced increases (P < .05) in serum concentrations of IGF-I, IGF-II, insulin, and glucose and decreases in urea nitrogen. Concentrations of pST 24 h after injection were lower (P < .05) in pST-injected pigs than in buffer-injected pigs, indicating negative feedback on endogenous pST secretion. The pST-induced increases (P < .05) in insulin, IGF-I, and IGF-II and the decrease in urea nitrogen were evident at 24 h after the initial injection. Although pST administration improved the growth performance and composition of lean and obese barrows and gilts, the influences of line and sex were not expunged by administration of pST.

Obesity and dehydroepiandrosterone/dehydroepiandrosterone sulfate relationships in lean, obese, and meat-type cross-bred boars: responses to porcine growth hormone.

As so many variables can affect obesity (age, genetics, health status), new directions, other than reducing or altering diet, are being pursued in controlling obesity in our society. Both dehydroepiandrosterone (DHEA) and GH have reported antiobesity effects; thus, the possible interaction of these hormones was investigated in genetically lean, obese, and meat-type cross-bred male pigs (boars) administered implants that released 0, 2, or 4 mg/day recombinant porcine GH (pGH) for 42 days. Subcutaneous fat was determined by measurement of back fat depth at 2-week intervals, and blood samples were obtained 0, 7, 14, 28, and 42 days post-implant. The weight of perinephrenic fat, an index of abdominal fat, was obtained at death. The obese line had higher DHEA/DHEA sulfate (DHEA-SO4) serum concentrations than the lean and cross-bred boars. Treatment with pGH reduced sc and perinephrenic fat in all lines at both doses (P < 0.01). There was no relationship between day 42 concentrations of DHEA/DHEA-SO4 and indexes of obesity. Concentrations of DHEA/DHEA-SO4 were decreased by pGH treatment (P < 0.01) by days 7-14 in all genetic lines. Concentrations of insulin-like growth factor I, insulin-like growth factor II, and insulin were increased with pGH treatment in all lines (P < 0.01). The a priori hypothesis that increases in these peptides would stimulate gonadal steroidal synthesis (as demonstrated in vitro) and result in elevated DHEA/DHEA-SO4 concentrations and reduced obesity was not supported by pGH-induced decreases in DHEA/DHEA-SO4. Insulin concentrations were elevated 7-14 days postimplant in all lines (P < 0.01), then declined in the later stages of the trial. Insulin concentrations and DHEA/DHEA-SO4 concentrations were inversely related (r = -0.59; P < 0.05); this may indicate that with elevated insulin levels, DHEA/DHEA-SO4 is decreased and has a limited opportunity to affect obesity. Although the administration of DHEA may reduce obesity, the lipolytic action of pGH does not appear to be through increased circulating concentrations of DHEA/DHEA-SO4.