97.Hormones & Farm Animal Growth

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97.Hormones & Farm Animal Growth

 

 

 

CATEGORY: Anabolic Steroids 100 Courses

COURSE NUMBER: 97

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Syllabus

1 Whole Animal Growth 1

Measuring Animal Growth 1

Embryonic and Fetal Growth 3

Growth Curves 4

Genetics, Nutrition and Environmental Effects

on Whole Animal Growth 6

Genetics 6

Nutrition 9

Environmental factors 10

2 Cellular and Molecular Biology 13

Prokaryotic and Eukaryotic Organisms 13

Eukaryotic cell organelles 14

The Cell Cycle 16

The Central Dogma of Cell Biology 18

Eukaryotic genes 19

Ribonucleic Acid 21

Messenger RNA and translation of protein 21

RNApolymerases 23

Regulation of gene transcription 24

Transcriptional control of specific genes 25

Transcription factors 26

Biotechnology and Genetic Engineering 27

Transgenic Animals and their Potential 28

Identifying, Isolating and Transferring Genes 28

Homologous recombination, gene targeting

and gene knockouts 33

3 The Endocrine System 37

Control of Pituitary Hormone Secretion 43

Hormone Receptors 46

Effector Molecules, Transducers and Second Messengers 48

4 Development of Muscle, Skeletal System

and Adipose Tissue 55

Embryonic Development and Cell Differentiation 55

Cell Proliferation and Differentiation 59

The Skeletal System and Bone Growth 60

Types of Bones and Gross Anatomy 61

Bone Cells and Bone Matrix Formation 61

Osteoclasts and bone resorption 64

Regulation of osteoclast function 65

The Epiphyseal Plate 67

Skeletal Muscle Development 68

Embryonic formation of skeletal muscle 68

Skeletal muscle satellite cells 69

Myofilaments, Myofibrils and Sarcomeres 71

Sarcomeric proteins: actin, myosin and titin 73

Myofibres and muscle contraction 74

Skeletal Muscle Fibre Types 77

Skeletal muscle protein turnover 79

The formation of multinucleated skeletal muscle cells 80

Adipose Tissue Growth and Development 82

Brown adipose tissue 82

White adipose tissue 83

Adipose tissue development 84

Adipose tissue growth: hyperplasia vs hypertrophy 85

Lipogenesis and Lipolysis 87

5 Growth Hormone and Insulin-like Growth Factors 94

The GH Molecule 94

Control of GH secretion 96

GH receptors 99

Metabolic actions of GH 101

Excess and inadequate GH: giants and dwarfs 104

IGFs or Somatomedins 105

Discovery of the IGFs 105

IGF genes and molecules 107

IGF receptors 108

IGF-binding proteins 110

Metabolic effects of the IGFs 111

Effects of the IGFs on animal growth 112

Modification of the somatomedin hypothesis 115

Effects of GH on Farm Animal Production 116

GH and the development of transgenic animals 119

6 Calcium Homeostasis

and Regulation of Bone Growth 123

Hormonal Regulation of Calcium Homeostasis 124

Parathyroid hormone 124

1,25-Dihydroxy vitamin D3 126

Biological actions of 1,25-dihydroxy vitamin D3 127

Calcitonin 129

Regulation of Bone Growth and Development 131

The hedgehogs and early skeletal differentiation 131

Regulation of bone growth and differentiation

by hormones 132

Growth factors and bone 135

FGF 135

PDGF 137

Transforming growth factor-β 140

Bone morphogenetic proteins 143

7 Hormones, Growth Factors and Skeletal Muscle 146

Experimental Systems to Study Myogenesis 146

Myogenic cell systems 147

Muscle Regulatory Factors (MRFs) 148

Effects of the MRFs on muscle development 150

Regulation of MRF expression 151

Growth Factors Affecting Muscle Growth 153

IGFs 153

Myostatin 155

FGF 156

TGF-β 156

BMPs 157

Hepatocyte growth factor 157

Hormones regulating muscle growth 158

8 Hormones, Growth Factors

and Adipose Tissue 163

Cell Systems Used to Study Adipogenesis 163

Transcription Factors and Adipogenesis 166

PPARs 167

C/EBPs 169

ADD1/SREBP1 170

Nuclear co-activators and co-repressors: fine-tuning the

adipogenic response 172

Hormones and Growth Factors Affecting Preadipocytes

and Adipocytes 173

Insulin 173

GH and the IGFs 174

Glucocorticoids 176

Prostaglandins and cAMP 176

Negative Regulators of Adipose Differentiation 177

Adipose tissue as an endocrine organ 178

Contents vii

9 Steroids and Animal Growth 181

Oestrogens and Ruminant Growth 183

Oestrogens and Non-ruminants 185

Androgens and Ruminant Growth 186

Mechanism of Action of Steroids in Ruminant Growth 187

Androgen mechanisms of action 188

10 Catecholamines, Beta-agonists and Nutrient

Repartitioning 191

The Autonomic Nervous System and the Adrenal Medulla 192

Adrenergic Receptors 195

β-Adrenergic agonists 198

Effects of β-adrenergic agonists on growth

and body composition 198

11 Leptin, Body Composition

and Appetite Control 202

Theories on the Short-term Regulation of Food Intake 204

The Long-term Regulation of Food Intake – the Lipostat Theory 205

The Discovery of Leptin 207

The leptin gene and molecule 207

Leptin receptors and binding proteins 208

Biological actions of leptin 210

Effects of leptin on reproduction 212

Direct peripheral effects of leptin 212

Regulation of leptin concentrations 213

Significance of leptin to animal production 213

Appetite-inducing (Orexigenic) Peptides of the Hypothalamus 214

Index  217

 

Hormones & Farm Animal Growth


Growth promoters including hormonal substances and antibiotics are used legally and illegally in food producing animals for the growth promotion of livestock animals. Hormonal substances still under debate in terms of their human health impacts are estradiol-17β, progesterone, testosterone, zeranol, trenbolone, and melengestrol acetate (MGA) . Many of the risk assessment results of natural steroid hormones have presented negligible impacts when they are used under good veterinary practices. For synthetic hormonelike substances, ADIs and MRLs have been established for food safety along with the approval of animal treatment. Small amounts of antibiotics added to feedstuff present growth promotion effects via the prevention of infectious diseases at doses lower than therapeutic dose. The induction of antimicrobial resistant bacteria and the disruption of normal human intestinal flora are major concerns in terms of human health impact. Regulatory guidance such as ADIs and MRLs fully reflect the impact on human gastrointestinal microflora. However, before deciding on any risk management options, risk assessments of antimicrobial resistance require large-scale evidence regarding the relationship between antimicrobial use in food-producing animals and the occurrence of antimicrobial resistance in human pathogens. In this article, the risk profiles of hormonal and antibacterial growth promoters are provided based on recent toxicity and human exposure information, and recommendations for risk management to prevent human health impacts by the use of growth promoters are also presented.


Veterinary drugs including antibiotics, growth hormones, and antihelminths are used for disease control and growth promotion of livestock animals. However, concerns regarding the safety of livestock products and the prevalence of antimicrobial resistance have grown according to the increased use of veterinary drugs.
Risk assessment is an integrative strategy to assume the probability of human illness caused by the ingestion of livestock products containing residual veterinary drugs. Both antimicrobials and growth hormones used for growth promotion in food-producing animals have provoked much debate on the safety of livestock products for human consumption. Many studies have been performed to estimate the real probability of human health impact. We need to understand the human health risks of antimicrobials and growth hormones under a framework basis composed of assessments of exposure amounts, dose-response relationships, and human illness consequences.


The major goal of this article is to illustrate methods for the risk assessment of growth hormones and antimicrobials and to provide the results of quantitative risk assessments of them based on current scientific knowledge and available data.


Veterinary drugs are a type of chemical hazard in foods of animal origin. Many of these substances are evaluated for their potency of human health impacts in case they remain in foods. The approval of veterinary drugs used in food-producing animals can be made after systemic evaluation of efficacy, target animal safety, human health risk, and environmental impacts. From the viewpoint of risk management, maximum residue limits (MRLs) are regarded as a monitoring tool for compliance to the approved conditions of use, and the ADI level is a decision point for human health impacts.


Risk assessments of veterinary drugs consist of assessing their toxicological and microbiological impacts and identifying acceptable consumption levels that the compounds should not exceed. Toxicological impact implies any biological adverse effects caused by direct intake of veterinary drugs, such as body weight change, immune suppression, and various disorders of normal body function. For microbiological impact, the targets of the ingested veterinary drugs are human intestinal microflora rather than the human body. Human intestinal microflora play important roles in the maintenance of human health. Major functions of gut microbiota for human health are: the metabolic fermentation of non-digestible dietary components and endogenous mucus, control of proliferation and differentiation of intestinal epithelial cells, development and homoeostasis of the immune system, and protection against exogenous pathogens (Shenderov, 1998) . Microbiological impact needs to be evaluated when the ingested residue compound is antimicrobiologically active, not transformed irreversibly to inactive metabolites, and enters the lower intestine by any administration route (JECFA, 2000a; Jeong et al., 2009) .Many veterinary antimicrobials are allotted into a class requiring microbiological risk assessment.


A wide range of scientific data is required to ensure certain veterinary drug can be used in a manner that does not have adverse effects on public health. Where appropriate, data should be generated in accordance with national or international Good Laboratory Practice (GLP) guidelines.


The data should cover acute toxicity; short-term toxicity; long-term toxicity; reproductive toxicity; carcinogenicity; genotoxicity; specific organ toxicity including immunotoxicity and neurotoxicity; endocrine disruption effects and impacts on human intestinal microflora; metabolism and depletion in target animals; and environmental fate.


Risk assessments of veterinary drugs residing in foods are performed by following the integrative steps of hazard identification, hazard characterization, exposure assessment, and risk characterization (WHO, 2004) . At the step of hazard identification, known or potential adverse health effects in humans are identified, which are induced by a veterinary drug or its metabolites that may be present in a particular food.
Toxicological evaluations, toxicokinetic assessments, and cancer/non-cancer evaluations are mainly performed for hazard identification. At the hazard characterization step, the characteristics of the adverse effects associated with a veterinary drug or its metabolites present in food are demonstrated. In addition, the levels that clearly do not cause any adverse effects on human health are evaluated according to dose-response relationships. NOAELs (no-observedadverse-effect-levels) , ADIs, benchmark doses at lower confidence limits (BMDLs) , uncertainty factors, and threshold levels for toxicological concern are drawn from the hazard characterization step. ADI is calculated by dividing the NOAEL with an uncertainty factor. When a veterinary drug or its metabolites are microbiologically active and can enter the lower intestine without inactivation, a microbiological ADI is assessed as well as a toxicological ADI. The lower ADI value is finally selected as the drug’s ADI (Table 1) . In case the chemical is evaluated as a complete carcinogen, which means a genotoxic carcinogen, it is recommended to operate a policy of prohibition and control levels “as low as reasonably practicable”


During exposure assessment, the likely intake amount of a veterinary drug or its metabolites pertaining to toxicological concerns along with exposures from other sources where relevant is estimated. The Estimated Daily Intake (EDI) amount is calculated using a nationally or internationally accepted approach. The EDI value of a veterinary drug is drawn by the sum of all values that are calculated by multiplying the median residue levels in food components with estimates of dietary intake. When groups of high risk consumers or sensitive populations responding to a specific veterinary drug are identified, the exposure amount is assessed more carefully. The approval of the usage of veterinary drugs is determined by comparing the EDI with the ADI. If the EDI is higher than the ADI, approval may not be possible or withdrawn.


At the step of risk characterization, estimations of the severity and occurrence of known potential adverse health effects in a given population are estimated based on hazard identification, hazard characterization, and exposure assessment. Evaluation of the risk caused by consumption in highly sensitive population groups can be performed when required in the viewpoint of public health. The margin of exposure (MOE) , margin of safety (MOS) , level of protection (LOP) ,and MRLs are determined at this step. A large margin of safety is generally posed, which leads to a level well below that which causes any toxic effects in animal studies. The actual intake of an approved substance is entirely lower than the estimated level for human health concerns because it is extremely unlikely that each and every item of consumed food over an individual’s lifetime will have been treated with a particular compound.


For risk management, it is the ADI not MRL that refers to human health-related risks by consuming a certain amount of veterinary drug via food intake. Data on toxicity and residue have been assessed and conditions are placed on their registration to ensure MRLs are not exceeded before the approval of veterinary drugs.
Inspection and surveillance of residues of veterinary drugs are very important regulation tools to secure food safety. However, it is not practical to monitor all items of suspected compounds in foods. Risk scoring for setting priorities in veterinary drug residue monitoring is recommended as an efficient strategy for risk management such that more intensified monitoring is applied for components having higher scores of potential risk. Risk is scored according to toxicological thresholds, estimated exposure amounts, the occurrence of antimicrobial resistance, violation frequency, and so forth.


Newly developed approaches including BMDL and MOE evaluations, EDI calculations, and mode of action (MOA) assessments provide more scientific and practical ways for risk assessment. The endeavor to make more reasonable and sound directions in the authorization of veterinary drugs, establishment of ADIs and/or MRLs, and scoring of risk priority may guarantee food safety via state-of-the-art health risk assessments and risk management advice, optimally attuned to consumer needs.

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