Growth Promoting Agents

Growth Promoting Steroids
The importance of the sex hormones, both androgens and oestrogens, in controlling fatness and growth is illustrated by the use of synthetic growth-promoting substances (anabolic steroids) based on them. Androgens have actions like the male sex hormone testosterone. Oestrogens have actions like the female sex hormone oestradiol. Progestagens act like the female hormone progesterone, the main physiological function of which is to suppress oestrus, and have been used to enhance the effects of the other sex hormones. Trenbolone acetate is a synthetic androgen that promotes growth by decreasing protein degradation in muscle. Similarly, the synthetic oestrogen zeranol also promotes growth by decreasing protein degradation. Both hormones therefore work by reducing protein turnover rather than by increasing protein synthesis. As might be expected, the effects of synthetic sex hormones depend to a degree on the sex of the animal to which they are administered since it is the balance of male and female hormones which is important. Females tend to respond better to androgens and males to oestrogens. Castrates tend to respond best to a combination of androgens and oestrogens. The use of anabolic sex steroids, usually as implants, was wide-
spread in cattle in Europe until banned in the EU (EU Directive 88/146/EEC). There was concern about the potential effects of steroid residues on humans who consumed the meat and offal from treated animals particularly if the recommended dose rates had not been adhered to. Nevertheless, the compounds are still in use in many countries outside the EU, including North America. Examples of anabolic sex hormone products are given in Table 2.10. Anabolic sex steroids are usually administered as compressed tablets implanted into
the tissues of the ear (a non-edible part of the animal). Other growth promoting steroids that have been used are the stilbenes (diethyl stilboestrol, hexoestrol) which were banned in the EU in 1981 and also North America, because of concerns, possibly unfounded, that they could cause cancer in people eating meat.

Nama Produk                               Hormon                                    ProdusenFinaplix®                              Trenbolone acetate                      Hoechst
Ralgro®                                Zeranol                                       Crown Cheodusmicals 
Compudose®                        Oestradiol                                   Elanco
Synovex S®                          Oestradiol + progesterone           Syntex  
Synovex H®                         Testosterone + oestradiol             Syntex  

Beta-Adrenergic agonists
A  class  of  pharmacological  compounds  that  has  shown  enormous potential  to  alter  the  muscularity  and  ratio  of  lean  to  fat  in  meat animals  is  the 
Beta-adrenergic  agonists. These  have  chemical  structures
similar  to  the  naturally  occurring  catecholamines,  adrenaline (epinephrine)  and  noradrenaline  (norepinephrine).  Adrenaline  and noradrenaline  are hormones  that  are  secreted  in  response  to  stressful
situations (see Chapter 10). Noradrenaline is also the neurotransmitter found  in  the  sympathetic  nervous  system  (equivalent  to  the acetylcholine of the parasympathetic system). Examples of
Beta-adrenergic agonists are clenbuterol, cimaterol, salbutamol and ractopamine. 

Beta Adrenergic  agonists  are  so  called because  they  act on  cells via  Betareceptors on the cell membrane. The Beta receptors can be subdivided into two types. Beta 1 receptors are characteristic of cardiac and intestinal muscle; Beta 2 receptors are characteristic of bronchial and uterine smooth muscle.  However,  both  Beta 1 and  Beta 2 receptors  occur  in  many  tissues including skeletal muscle and fat. The Beta -adrenergic agonists of interest in animal production mainly affect Beta 2 receptors but the classification into Beta 1 and Beta 2 is not clear-cut and some Beta 1 activity is also evident. The potential value of Beta -adrenergic agonists in meat animals lies in their so-called repartitioning effects. They reduce the amount of fat in the  body  and  increase  protein  accretion  so  promoting  muscular development. They appear to do this by both reducing the production of  fat  (lipogenesis)  and  increasing  fat  breakdown  (lipolysis; Cardoso and Stock, 1998). Their action on protein accretion seems to be through reducing  breakdown,  so  favouring  the  synthesis  component  of  the normal protein turnover. Some muscles, particularly those with a high proportion of type II, glycolytic, fast contracting fibres (see Chapter 3), are  more  affected  than  others.  Although  they  influence  circulating levels of insulin, growth hormone and the thyroid hormones, it is not thought that the effects of Beta-adrenergic agonists are mediated through these. Unlike anabolic steroid hormones, Beta-adrenergic agonists are effective in  all  sexes  to  the  same  extent.  They  are  orally  active  and  so  can  be administered  in  the  feed, usually  at  levels  of  between  1  and  10 ppm. They are therefore effective at very low doses. Although they may show small effects on growth rate this is not a consistent effect and is generally more  apparent  in  ruminants  than  in  non-ruminants.  Carcass  yield  is improved by around 1–2%  in pigs and poultry and by up  to 5–6%  in cattle and sheep. There is evidence that this is due to both an increase in carcass weight and a decrease  in  the size of  the viscera. The carcasses have  better  conformation.  The  increases  in  muscle  development  are accompanied  by  reductions  in  subcutaneous,  intermuscular  and  intra-muscular  fat. The effects of administration of a Beta-adrenergic agonist  to pigs are illustrated in Table 2.11. A comparison of the effects of treatment with Beta-adrenergic  agonists  on pigs  and  sheep  is  shown  in Table  2.12. These figures illustrate the potential gains to be had from administration of  Beta-adrenergic  agonists.  However,  the  gains  are  offset  by  potentially poorer meat quality. Some Beta-adrenergic agonists may produce meat thatis  darker  and  duller  in  colour,  and  tougher  after  cooking.  The  darker colour is caused by reduced glycogen levels in the muscles at slaughter leading  to  a higher ultimate pH  in  the muscles. Toughness may  result from  a  lower  activity of proteolytic  enzyme  systems post mortem (see Chapter 5). By reducing intramuscular fat, Beta-adrenergic agonists may also reduce other eating quality characteristics.