Interactive effect of exercise training and growth hormone administration on histopathological and functional assessment of the liver in male Wistar rats.

BACKGROUND: Abuse of growth hormone (GH) is expanding in exercising populations due to its lipolytic and anabolic actions. The purpose of this study was to examine the interactive effect of exercise training and GH administration on histopathological and functional assessment in the liver of male Wistar rats. METHODS: Forty-eight male Wistar rats were randomly divided into six groups including control + saline group (CS), GH injection group (GI), resistance training + saline group (RS), aerobic training + saline group (AS), resistance training + GH injection group (RG), aerobic training + GH injection group (AG). All groups were injected with either saline or GH 1 h before each training session. RT and AT were performed five days/week for a total of 8-weeks. At the end of the study, blood samples and liver tissue samples were taken to evaluate circulating AST, ALT, and ALP enzymes, as well as albumin protein. Histopathology of liver tissue was performed via qualitative microscopic evaluation. RESULTS: Microscopic evaluation of liver tissue did not show any histopathologic changes. All the groups administered with GH showed a significant increase in ALT, ALP, and albumin protein (P<0.05). However, AST enzyme concentrations increased significantly only in the RG group (P=0.022). In addition, neither RS nor the AS groups showed significant AST, ALT, and ALP changes, but serum albumin concentration significantly increased in the AS group (P=0.033). CONCLUSIONS: The elevation of liver enzymes showed that GH administration with or without exercise training might cause severe liver damage.

An assessment of androgenic/anti-androgenic effects of GH transgenic carp by Hershberger assay.

OBJECTIVE: To evaluate the androgenic and anti-androgenic effects of GH (growth hormone) transgenic carp in male rats. METHODS: Hershberger assay was carried out in castrated male SD rats aged 4-5 weeks. Testosterone propionate (TP) (0.4 mg/kg BW) was administrated for a positive control, GH transgenic carp (3.0 g/kg BW)+TP (0.4 mg/kg BW), parental carp (3.0 g/kg BW) + TP (0.4 mg/kg BW), and flutamide (Flu) (3.0 g/kg BW) were used for negative controls, and vehicle was administered orally for a blank control. All groups were administrated for 10 consecutive days. At the end of the test, animals were anesthetized, then weights of accessory sex organ were measured. Serum testosterone (T), luteinizing hormone (LH), and Follicle-Stimulating Hormone (FSH) levels were detected. RESULTS: The weights ratios of the accessory sex organs and body weights showed no significant differences between the solvent control and the GH transgenic carp-treated groups. Serum concentrations of FSH, LH, and T of the rats treated with GH transgenic carp + TP showed no significant changes, compared with those treated with TP only. CONCLUSION: GH transgenic carp does not have any androgenic agonist or antagonist properties in vivo screening tests.

Induced lactation in pubertal heifers: efficacy, response to bovine somatotropin, and profitability.

Heifer rearing represents one of the largest costs of commercial dairying because these animals do not begin to produce milk until approximately 2 yr of age. The objectives of this study were to characterize milk production, growth, reproduction, and herd life after induced lactation in healthy 15-mo-old heifers. We further wanted to quantify their lactation response to bovine somatotropin (bST), and compare survival rate and profitability of heifers induced into lactation to that of heifers reared using traditional methods. Holstein heifers (n = 32) were induced into lactation by administration of estradiol-17ß (0.075 mg/kg of body weight per d) and progesterone (0.25 mg/kg of body weight per d) for 7 d. Milking began on experimental d 18. Heifers were paired based on milk production, and one in each pair was assigned randomly to bST or control treatment groups; treatments began on 25 ± 7 d of lactation, and milk production was compared for 70 d. Heifers treated with bST produced 14.7% more milk than did controls. After the 70-d comparison period, all heifers received bST for the remainder of their lactations. Throughout the induced lactation, heifers gained 0.69 kg/d, averaged 1.8 services/pregnancy, and 27 heifers calved for a second lactation. For the herd life and economic analyses, heifers induced into lactation were compared with similarly aged heifers in the same herd reared by traditional management methods. The animals induced into lactation had a 62.7% chance of remaining in the herd as long as the peer cohorts, but both groups had similar productive lifespans. Net present value for an induced animal ($2,459) was not different from that of a traditionally raised peer ($3,137). In summary, heifers hormonally induced into lactation with estrogen and progesterone were healthy, grew normally, had a mean daily milk production of 18 kg with normal composition, and had good reproductive performance. Based upon the assumptions and prevailing financial environment of this experiment, hormonally induced lactation of 15-mo-old heifers, as a routine management tool, was not more profitable than traditional management practices.

Development of a metabonomic approach based on LC-ESI-HRMS measurements for profiling of metabolic changes induced by recombinant equine growth hormone in horse urine.

Despite the worldwide existing regulation banning the use of the recombinant equine growth hormone (reGH) as growth promoter, it is suspected to be used in horseracing to improve performances. Various analytical methods previously developed to screen for its misuse have encountered some limitations in terms of detection timeframes, in particular during the first days following reGH administration. A novel strategy involving the characterization of global metabolomic fingerprints in urine samples of non-treated and reGH-treated horses by liquid chromatography-electrospray-high-resolution mass spectrometry (LC-ESI-HRMS) is described and assessed in this paper in order to develop a new screening tool for growth hormone abuse in horseracing. The strategy involves a limited sample preparation of the urine samples and the use of appropriate software for data processing and analysis. As preliminary work, reproducibility of both sample preparation and mass spectrometry (MS) measurements was evaluated in order to demonstrate the reliability of the method. Application of the developed protocol on two horses demonstrated the suitability of the developed strategy and preliminary results showed significant modifications of the metabolome after treatment with reGH.

Recombinant rat and mouse growth hormones: risk assessment of carcinogenic potential in 2-year bioassays in rats and mice.

Recombinant rat growth hormone (rrGH) and recombinant mouse growth hormone (rmGH) were developed to evaluate the potential carcinogenicity of each biologically active growth hormone (GH) as assessed in the respective species. Biological activities of rrGH and rmGH were demonstrated by showing an increase in body weight gain and serum levels of insulin-like growth factor-1 (IGF-1) in hypophysectomized rats receiving daily sc injections for 6 days. With the exception of pharmacologically mediated weight gain, rrGH and rmGH had no adverse effects in 5-week oral toxicity studies and no production of anti-recombinant GH antibodies. The high doses selected for the carcinogenicity studies provided systemic exposures of GH up to approximately 10-fold over basal levels. In the 105-week mouse carcinogenicity study, daily sc injections of rmGH at 0.1, 0.2, or 0.5 mg/kg/day were well tolerated and had no effects on survival or incidence of tumors. In the 106-week rat carcinogenicity study, daily sc injections of rrGH at 0.2, 0.4, or 0.8 mg/kg/day had a favorable effect on longevity in female rats administered 0.4 or 0.8 mg/kg/day, an increased weight gain in females and males, and no increase in the incidence of tumors. The absence of carcinogenic effects of recombinant GH administered daily for 2 years to rodents was consistent with publications of clinical experience, indicating a lack of convincing evidence for an increased risk of cancer in children receiving human recombinant GH replacement therapy.

Welfare effects of the use of recombinant bovine somatotropin in the USA.

The welfare effects of increased milk production associated with the use of recombinant bovine somatotropin (rBST) on dairy operations in the USA were examined for 1996. Results that derived from three different estimates of the milk-production response to rBST were evaluated and compared. One estimate, derived from a survey of dairy producers in Connecticut, led to economic-impact estimates that were not statistically significant. A second, derived from a national survey that concentrated on the health and management of dairy cattle, led to estimates that were unbelievably high. A third, derived from a national survey that concentrated on the economics of dairy producers, provided the most reasonable estimates of economic impacts. Results of economic analysis, using the latter results, indicated that if rBST had not caused milk production to increase, then the market price of milk would have been 2.2 +/- 1.5 cents/kg higher, and the total value of the milk produced would have risen from Dollars 23.0 +/- 0.6 billion to Dollars 24.1 +/- 1.0 billion. A welfare analysis demonstrated that the increased milk production (and the reduced market price) associated with the use of rBST in the USA caused the economic surplus of consumers to rise by Dollars 1.5 +/- 1.0 billion, while the economic surplus of dairy producers fell by Dollars 1.1 +/- Dollars 0.8 billion. Increased milk production associated with rBST yielded a total gain to the US economy of Dollars 440 +/- 280 million. An analysis of annual percent changes in the number of dairy cows per operation, milk production per cow, total milk production, total number of dairy cows, and total number of dairy operations in the USA suggested that the dairy industry's long-term economic growth path was stable from 1989-2001 inclusive, and did not receive a shock resulting from the introduction of rBST.

Can we increase adolescent growth?

Adolescent growth represents 15-20% of adult height and has been the focus of several treatment interventions, aiming at increasing the amplitude of the adolescent spurt. Importantly, pre- and early puberty are times when patients and families seek medical help and when estimates of adult height are more accurate than in younger children. We review the current approaches aimed at increasing pubertal growth in short children and knowledge about their results and risks. GnRH agonists, when used outside the context of precocious puberty, induce a modest gain (4 cm) when they are used for more than 3 years. Their effects on bone mass, body composition and possibly on psychosocial parameters limit their use. Several trials have now shown that GH can increase adult height of short adolescents with idiopathic short stature or born small for gestational age. However, the amplitude of the effect is modest and of dubious clinical significance. Lastly, the association of both approaches is rather popular among pediatric endocrinologists but still lacks a definite demonstration of its efficacy. In conclusion, we have gained insight in the median effects of some of these treatments and overoptimistic initial expectations are now refocused. However, we still have a long way to go before we truly evaluate the factors affecting the variable individual responses to these treatments, their clinical significance and their cost-benefit balance.

STAT 5 activators can replace the requirement of FBS in the adipogenesis of 3T3-L1 cells.

The 3T3-L1 cells differentiate into fat cells that have many properties of native adipocytes including: substantial lipid accumulation, insulin sensitivity, and the ability to secrete endocrine hormones. A substantial expense in using these cells is fetal bovine serum (FBS), a critical component of efficient adipogenesis. Our recent studies on STAT 5 proteins have revealed that these transcription factors are phosphorylated and translocate to the nucleus immediately after the initiation of differentiation. Studies by several other laboratories also suggest that STAT 5 proteins can have pro-adipogenic properties. Growth hormone (GH) and prolactin (PRL) are both potent activators of STAT 5A and STAT 5B proteins. Since, FBS has high concentrations of GH; we examined the ability of GH to replace FBS as a component of the differentiation cocktail for 3T3-L1 cells. Our studies revealed that FBS was not required for the adipogenesis of 3T3-L1 cells if GH or PRL was added to the differentiation cocktail. Adipogenesis was judged by Oil Red O staining and expression of adipocyte marker genes. Hence, we have developed a substantially less expensive method for differentiating 3T3-L1 cells without FBS, thiazolidinediones, or expensive cytokines.

Effect of modified dry period lengths and bovine somatotropin on yield and composition of milk from dairy cows.

Dry periods of 40 to 60 d have been an industry standard because dry periods <40 d have resulted in reduced milk yields in the subsequent lactation by 10 to 30%. However, recent research has demonstrated no production losses for cows given a 30-d dry period. The current study evaluated milk production effects of shortened or omitted dry periods for cows at mature-equivalent production >12,000 kg of milk and treated with bovine somatotropin (bST). The study used 2 commercial dairies and one university dairy and included 4 treatments. Five multiparous and 5 primiparous cows from each farm were assigned to each treatment: 1) 60-d dry period, label use of bST (60DD); 2) 30-d dry period, label use of bST (30DD); 3) continuous milking, label use of bST (CMLST); and 4) continuous milking with continuous use of bST (CMCST). Per label, bST use started at 57 to 70 d in milk and ended 14 d before drying (60DD and 30DD) or expected calving date (CMLST). In primiparous cows, average milk yields during the first 17 wk of lactation were reduced for cows on treatments 30DD, CMLST, and CMCST vs. the 60DD treatment. (38.3, 35.1, and 37.5 vs. 44.1 +/- 1.3 kg/d, respectively). For multiparous cows, respective milk yields did not differ (46.6, 43.4, 46.5, and 47.7 +/- 2.1 kg/d). Shortened or omitted dry periods may impede mammary growth in primiparous cows, resulting in reduced milk yield in the subsequent lactation. In contrast, a shortened or omitted dry period with either bST protocol did not alter production in multiparous cows treated with bST. Quality aspects of prepartum milk and colostrum require additional characterization. For multiparous cows, milk income generated for short dry periods or for continuous milking might increase their profitability. At 17 wk of the subsequent lactation, estimates of the cumulative net margins of multiparous cows on the 30DD treatment and continuous milking treatments exceeded those of cows on the 60DD treatment by 40 dollars to 60 dollars per cow.

Nutritional assessment of somatolactin function in gilthead sea bream (Sparus aurata): concurrent changes in somatotropic axis and pancreatic hormones.

The role of somatolactin (SL) in the regulation of energy homeostasis in gilthead sea bream (Sparus aurata) has been analysed. First, a down-regulation of plasma SL levels in response to gross shifts in dietary amino acid profile and the graded replacement of fish meal by plant protein sources (50%, 75% and 100%) has been observed. Thus, the impaired growth performance with changes in dietary amino acid profile and dietary protein source was accompanied by a decrease in plasma SL levels, which also decreased over the course of the post-prandial period irrespective of dietary nitrogen source. Secondly, we examined the effect of SL and growth hormone (GH) administration on voluntary feed intake. A single intraperitoneal injection of recombinant gilthead sea bream SL (0.1 microg/g fish) evoked a short-term inhibition of feed intake, whereas the same dose of GH exerted a marked enhancement of feed intake that still persisted 1 week later. Further, we addressed the effect of arginine (Arg) injection upon SL and related metabolic hormones (GH, insulin-like growth factor-I (IGF-I), insulin and glucagon) in fish fed diets with different nitrogen sources. A consistent effect of Arg injection (6.6 micromol/g fish) on plasma GH and IGF-I levels was not found regardless of dietary treatment. In contrast, the insulinotropic effect of Arg was found irrespective of dietary treatment, although the up-regulation of plasma glucagon and glucose levels was more persistent in fish fed a fish meal based diet (diet FM) than in those fed a plant protein diet with a 75% replacement (diet PP75). In the same way, a persistent and two-fold increase in plasma SL levels was observed in fish fed diet FM, whereas no effect was found in fish fed diet PP75. Taken together, these findings provide additional evidence for a role of SL as a marker of energy status, which may be perceived by fish as a daily and seasonal signal of abundant energy at a precise calendar time.

Induced lactation in nonpregnant cows: profitability and response to bovine somatotropin.

Significant culling of high-producing cows with low fertility reduces profitability of dairy farms as those cows are replaced with heifers. Induced lactation of nonpregnant cows may be a management alternative to reduce culling and increase profits. The objectives of this study were to evaluate the efficacy of bovine somatotropin (bST) to increase milk production in cows induced into lactation with estrogen plus progesterone, and to determine the profitability of inducing cows into lactation vs. using replacement heifers entering the herd as first-lactation cows. Parity 1 or greater, nonpregnant, healthy Holstein cows (n = 28) were induced into lactation by administration of estradiol-17beta (0.075 mg/kg of body weight [BW] per d) and progesterone (0.25 mg/kg of BW per d) for 7 d. Milking began on d 18. Cows were randomly assigned to control or bST treatment groups on d 37 +/- 20 of milking, and milk production was compared for 70 d. After the 70-d comparison, all cows received bST for the duration of lactation. Cows receiving bST produced more milk (28.4 kg/d) than controls (24.1 kg/d), with variable yields among cows. For the economic analysis, induced cows were compared to first-lactation cows in the same herd using fair market value for costs and multiple component pricing for milk. Net present value for an induced cow (1966 dollars) was significantly greater than that for a first-lactation cow (1446 dollars). Our data suggest that bST use in induced cows is profitable. If a reliable method were developed and approved by the FDA, inducing nonpregnant cows into lactation could be used by dairy producers to increase profitability.

Growth hormone abuse in the horse: preliminary assessment of a mass spectrometric procedure for IGF-1 identification and quantitation.

Previous studies have shown that insulin-like growth factor 1 (IGF-1) is a promising marker for the detection of growth hormone (GH) abuse in the horse. The significant increases observed with GH administration in comparison to natural levels imply the possibility of setting a threshold level for IGF-1 that would be indicative of GH abuse. Although an immunoradiometric assay (IRMA) has been identified as a reliable screening method, a more specific IGF-1 quantification method needs to be developed for the prosecution of GH abuse by horseracing authorities. This study describes such an HPLC electrospray mass spectrometry (LC/ESI-MS) method that was developed and then assessed for the specific analysis of IGF-1 at the low levels encountered in serum. The structural identity of IGF-1 was confirmed by endoproteinase Asp-N digestion followed by LC/MS and LC/MS/MS characterisation. This was followed by quantification of IGF-1 as the intact molecule against an internal standard.

Morphological assessment of the effect of growth hormone on preantral follicles from 11-day-old mice in an in vitro culture system.

The present study was carried out to verify that the cells attached to the outside of the basement membrane of mechanically isolated follicles are theca cells and to evaluate the effect of growth hormone (GH) on these cells. Preantral follicles, 100-140 micrometer in diameter, were mechanically isolated from 11-day-old BDF1 hybrid immature mice, divided randomly into two groups, and cultured in vitro. One group was treated with 0.1% collagenase immediately after mechanical isolation in an attempt to remove theca cells attached to the outside of the basement membrane. The other group was untreated. Morphological examination revealed that 86.1% of mechanically isolated follicles before collagenase treatment had at least one theca cell around the basement membrane on the single section. However, after collagenase treatment no theca cells remained on the basement membrane of the follicles. Androstenedione secretion as a result of stimulation by 100 ng/ml hCG was significantly higher in the culture medium of the follicles with theca cells than in those of collagenase-pretreated follicles (p < 0.0001), indicating that the cells attached to the outside of the basement membrane were actually functional theca cells, not interstitial cells. To elucidate the effect of GH on theca cells, preantral follicles cultured in the presence of 1.0 mIU/ml GH were morphologically examined. Preantral follicles mechanically isolated from immature mice showed significant proliferation of not only granulosa cells but also theca cells in the presence of GH. In particular, theca cells, which remained dotted on the basement membrane in a small number just after isolation, proliferated and finally formed complete layers after the culture with GH. This is the first report that GH induced the proliferation of theca cells to form morphologically complete layers around the preantral follicle from 11-day-old mice.

The role of food ethics in food policy.

Certain developments in the agricultural and food sciences have far-reaching implications for society and the environment, which suggest the need to examine their ethical acceptability as a standard component of technology assessment. Such considerations have led to the emergence of a new academic discipline, food ethics. The present paper describes how ethical theory may be applied to the analysis of the impacts of prospective food biotechnologies to assess potential effects on four 'interest groups', i.e. consumers, producers, treated organisms and the biota (fauna and flora). The principles which structure the framework used, i.e. the ethical matrix, are adapted to the field of agriculture and food from those applied in medical ethics. Use of the ethical matrix is illustrated by applying it to the specific case of bovine somatotrophin, the genetically-engineered protein hormone which is injected into lactating cattle to increase their milk yields. Ethical analysis is seen to depend on a number of critical requirements, i.e. scientific data, non-scientific evidence and predictions, suitably-qualified assessors ('competent moral judges'), the 'world-views' of the assessors and application of the precautionary principle to cope with 'uncertainty'.

Growth hormone: current and future therapeutic applications.

The increased availability of growth hormone (GH) in the mid-1980s, as a result of advances in recombinant DNA techniques, has allowed research into the use of this hormone at physiological dosage, as replacement therapy for adults with GH deficiency (GHD) and at pharmacological dosages as a possible therapeutic agent, for a number of disease states. GHD adults have increased body fat and reduced muscle mass and consequently, reduced strength and exercise tolerance. In addition, they are osteopenic, have unfavourable cardiac risk factors and impaired quality of life. In these individuals, replacing GH reverses these anomalies, although it may not alter the reduced insulin-sensitivity. A proportion of adults with GHD perceive a dramatic improvement in their well-being, energy levels and mood following replacement. GH has protein and osteoanabolic, lipolytic and antinatriuretic properties. GH has been considered for the therapeutic treatment of frailty associated with ageing, osteoporosis, morbid obesity, cardiac failure, major thermal injury and various acute and chronic catabolic conditions. Initial small, uncontrolled studies for many of these clinical problems suggested a beneficial effect of GH, although, later placebo-controlled studies have not observed such dramatic effects. Furthermore, with a recent publication demonstrating an approximate 2-fold increase in mortality in critically ill patients receiving large doses of GH, the use of GH should remain in the realms of replacement therapy and research, until there are significant advances in our understanding.

Effects of diet and bovine somatotropin on heifer growth and mammary development.

Forty Holstein heifers [body weight (BW) = 126 kg] were blocked by BW into groups of 4, and, within each block, heifers were randomly assigned to one of four treatments. Twenty heifers had ad libitum access to a diet formulated to produce a BW gain of 0.8 kg/d (control diet), and 20 heifers had ad libitum access to a diet formulated to produce a BW gain of 1.2 kg/d. (high diet). Half of the heifers fed each diet were injected daily with bovine somatotropin (bST; 25 micrograms/ kg of BW). The high diet increased daily BW gain as well as body condition score. Injection of bST also increased daily BW gain, but did not affect body condition score. The high diet reduced age at puberty by 58 d, but did not affect BW, withers height at puberty, or pelvic area at slaughter. Injection of bST had no effect on age at puberty, but increased BW, withers height at puberty, and pelvic area at slaughter. The high diet did not affect mammary parenchymal DNA, RNA, or the ratio of RNA to DNA. The injection of bST increased mammary parenchymal DNA, RNA, and the ratio of RNA to DNA. The high diet was more cost effective for rearing dairy heifers from 120 d of age to potential breeding size (> or = 363 kg of BW and postpubertal) than was the control diet. In conclusion, the high protein, high energy diet increased growth rate without detrimental effects on mammary development. Injection of bST increased BW, skeletal size, and mammary development.

Assessment of recombinant bovine somatotropin as an immunomodulator during avian coccidiosis: immunization with living oocysts.

Coccidiosis, a disease of great economic importance to the poultry industry, is generally controlled prophylactically by additions of anticoccidial drugs to the feed. However, increasing development of drug-resistant coccidia species has stimulated searches for alternative control methods, one of which is vaccination. As part of this effort, recombinant bovine growth hormone (rbST) was tested as a possible immune stimulator in combination with live oocyst vaccination. At a dose of 0.045 mg per chick, given by s.c. injection at 1 d of age, rbST did not improve immunity developed by immunization with 500 or 2,500 oocysts of Eimeria maxima as judged by weight gain and lesion scores. At a single dose of 0.09 mg per chick given at 1 d of age in combination with IMMUCOX, rbST provided some protection against challenge infection with Eimeria tenella but not Eimeria acervulina as judged by reduction in lesion scores. Treatment with 0.09 mg rbST per chick alone at 1 and 3 d of age was protective against challenge with E. tenella but not E. acervulina or E. maxima as judged by reduction in lesion scores. These results strongly indicate that rbST can act as an immune modulator in chickens infected with coccidia, and provide a basis for further investigations of its use as a vaccine adjuvant.

Ergogenic drugs in sports.

This article provides the practicing physician with an account of the commonly used ergogenic substances. Specific agents discussed include the following: stimulants, narcotic analgesics, anabolic-androgenic steroids, beta-blockers, diuretics, growth hormone, other peptide hormones, blood doping, and erythropoietin.

The empirical impact of bovine somatotropin on New York dairy farms.

Data from 259 farms that participated in the Cornell University Dairy Farm Business Summary Project were used to measure the impact of bovine somatotropin (bST) on milk production and profitability per cow. Linear regression was used to estimate the response to bST when other variables were held constant. Bovine somatotropin was a dummy variable for bST use or nonuse in the equations. For farms that used bST on 25% or more of the cow days in 1994, milk production increased by 510 kg per cow. Returns above purchased feed costs increased $153 per cow for farms that used bST. Milk receipts over operating costs increased $120 per cow for farms that used bST. The use of bST was estimated to increase net farm income by $27 per cow, but this estimated coefficient was not statistically different from 0. Differences in costs for labor or veterinary services per cow were not significantly different between farms that used bST and farms that did not use bST.