Endocrinology and Pharmacology

Experimental demonstration of endocrine effects on body composition is extensive.[7,8] For example, excess gluco-corticoid hormones produce decreased muscle and increased fat deposition. Insufficient thyroid hormone leads to excess fat production. Sex hormones have marked effects on body composition with mammalian males being more muscular and less fat than females or castrated males. However, because of aggressiveness and sexual activity, males are usually castrated. In some countries, male pigs are raised but are marketed at a younger age to avoid behavioral problems and boar-taint (an off-flavor developing with sexual maturity). In the United States,

Table 1 Effect of somatotropin and p adrenergic agonists in lambs

Variable

Somatotropina

ß-Adrenergic agonistsb

Gain

+ 14

+ 22

Feed/gain

- 22

-14

Protein g/d

+ 36

+ 12.2

Fat g/d

- 30

- 20

aAdapted from Table 2 of Ref. 7. bAdapted from Table 4 of Ref. 7.

aAdapted from Table 2 of Ref. 7. bAdapted from Table 4 of Ref. 7.

cattle are regularly implanted with sex steroids to augment growth and favor muscle production.[7,8]

Exogenous somatotropin (growth hormone) leads to increased muscle and visceral organ growth (Table 1), along with decreased fat deposition and feed intake.[7,8] Somatotropin is used to promote efficient muscle production in some countries. Experimental strategies stimulate endogenous somatotropin production or release through growth hormone releasing hormone or by decreasing activity of somatostatin (that is, diminishing somatotropin release). Insulin-like growth factor 1 (IGF-1) may be the mediator of many somatotropin effects, so its regulation can also control body composition. Selected compounds that stimulate b-adrenergic receptors (bAR agonists) increase muscle and decrease fat deposition (Table 1) with little effect on visceral growth and usually a decrease in feed consumption.[7,8] The pAR agonists are used in cattle and pigs in some countries.

In addition to the administration of exogenous hormones or synthetic analogs, endocrine function can be controlled by immunological approaches. Animals can be immunized against a peripheral endocrine substance to decrease its circulating levels or against a pituitary factor that modifies peripheral production and release of hormones. An example is the immunocastration of male mammals, wherein intact males can be raised to take advantage of the favorable growth characteristics and then they can be neutered by immunocastration to eliminate the later ensuing negative aspects of male behavior.

Using molecular biology techniques, transgenic animals that produce an excess of the transgene product have been created; animals with nonfunctional genes produce less of the gene product. Pigs were made transgenic for somatotropin.1-9-1 The approach has not become practical because the expression of the gene is irregular and variable in different tissues. As the function of gene promoters (that part of the gene that controls expression or production of messenger RNA and subsequent protein synthesis) and tissue-specific expression of genes is better understood, it is expected that these techniques will have practical value in animal production. An intriguing approach is a gene therapy that implants a DNA construct for growth hormone releasing hormone (GHRH) in skeletal muscle.[10] This construct then functions to produce and secrete GHRH. In the central nervous system GHRH causes release of somatotropin with consequent increase in IGF-1, an increase in muscle, and a decrease in fat mass. Thus, administration of exogenous somatotropin is avoided with its negative consumer biases. Other molecular biology approaches will present themselves in the future as the control of gene function is understood and methods are devised to selectively stimulate or disengage gene function in a specific tissue at particular times. Increased or decreased production of a hormone or growth factor at select times during growth will be possible. It should be possible to decrease fat synthesis or increase fat mobilization or oxidation at stages when these functions are less critical to the animal and over-function or under-function leads to excess fat deposition.

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