Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1999-07-08
2003-08-26
Le, Long V. (Department: 1641)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S004000, C435S287200, C435S810000, C436S063000, C436S164000, C436S501000, C436S518000, C436S536000, C436S811000, C436S817000, C424S130100, C424S158100, C424S520000, C424S529000, C424S530000, C424S531000, C530S399000
Reexamination Certificate
active
06610496
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a method for predicting animal growth performance, which includes administering a suitable amount of growth hormone releasing hormone (GHRH) to an animal, observing levels of growth hormone (GH) subsequent to GHRH administration and; predicting growth and fat development in an the animal from observed levels of GH. The invention also relates to a test kit for practicing the method of the invention.
BACKGROUND OF THE INVENTION
Beef currently accounts for 58% of all red meat consumed in the United States, constituting over $50 billion in retail value (1). Thus, beef production is a major contributor to the agricultural economy of the U.S., and its sustained and improved competitiveness is imperative. There is increasing consumer demand for leaner beef due to concerns over saturated fat consumption (2). Also excess fat accumulation on carcasses represents wasted resources of producers and cost to the packer. Producers, therefore, are interested in methods to decrease the fat content of beef while maintaining and improving the rate of gain. These two goals can at times be in conflict.
A path to improvement in both areas is to enhance the ability to select bulls of superior genetic potential for rapid, lean gain. Because over 90% of the beef cattle in the U.S. are bred by natural service, such a selection procedure would involve a large number of animals. Indeed, there are approximately 11,000 bulls selected each year on an official “bull test” at a cost of $300 to $400 per bull (3). A simple, accurate method to select bulls early in life for rapid, lean gain has tremendous potential to save producers money, increase the rate of genetic improvement, and provide consumers with a healthier product.
It is a common practice to select animals based on growth performance. The process is conducted under controlled feeding conditions. Limitations to this approach include the duration of time to obtain usable results, limited information on composition of gain, and the expense per animal.
Recently, interest has focused on identification of “growth” genes and their use in Marker Assisted Selection schemes. Indeed, a number of polymorphisms have been identified in genes of the bovine somatotrophic axis, including growth hormone (GH) (5-7), GH-receptor (8,9), and GH-releasing hormone (GHRH; 10). The impact of these polymorphisms on growth, however, has been less well defined. That is, little association has been made between specific sequence variations and subsequent physiologic responses and compositional data.
In contrast to genetic data, there is considerable information available attempting to correlate physiologic variables, such as spontaneous GH release with production and carcass endpoints (11-18). However, there has been considerable inconsistency in the utility of unstimulated GH as a selection criterion. Thus, recent efforts in dairy cattle have focused on the use of responses to GHRH, a specific stimulator of GH release and synthesis (19-21). Such an approach decreases variability associated with environmental factors and represents a more accurate index of an animal's ability to secrete GH than an acute, unstimulated sample. It is well established that GH is intimately involved in the process of growth and lean mass accretion in particular. Indeed, hypophysectomy of rats and other animals leads to a reduction in growth (26). Total reversal of this effect of hypophysectomy occurs only when GH is replaced (26). In cattle, immunological hypophysectomy via active immunization against GHRH results in marked reductions in circulating GH and IGF-1 as well as smaller, fatter animals (32,33). There is slight or no correlation between growth and mean concentrations of GH in cattle (12). Klindt et al. (11) found no correlation between characteristics of pulsatile GH release and growth in lambs. In contrast, in lambs that were selected for fat or lean carcass composition, lean lambs exhibited differences in pulsatile GH release and tended to have higher mean circulating GH concentrations (18). It is quite possible that external factors that affect GH secretion varied among these experiments, and such variability masked any true differences. Nevertheless, it appears that basing selection decisions on spontaneous GH would be of limited value.
In contrast to growth, there is a significant relationship between spontaneous GH secretion and milk production in cattle. Higher circulating GH is observed in dairy cows selected for superior milk production (15,17), and certain aspects of pulsatile GH release were observed to be positively correlated with genetic potential in dairy bulls (14). Disadvantages, such as environmental factors, remain a limitation to application of GH quantification in selection for genetic merit.
The hypothalamic hormone growth hormone-releasing hormone (GHRH) stimulates anterior pituitary gland secretion of GH, which increases lipolysis and, via IGF-1, promotes protein synthesis and growth of long bones. Exogenous GH increases rate of gain and decreases carcass fat percentage in cattle (Groenewegen et al., 1990; Binelli et al., 1995) and lambs (McLaughlin et al., 1994) and increases milk yield in dairy cows (Bauman et al., 1985). Administration of GHRH to lambs improves growth rate and lean gain (Beerman et al., 1990) and increases milk production in dairy cows (Dahl et al., 1991, 1993).
Problems and environmental influences are exacerbated in beef production systems because the range of environmental conditions that animals are exposed to is greater due to the quantity of animals maintained for natural service.
In an attempt to minimize environmental influences on selection, a robust method developed in dairy bulls associates GrH responses to GHRH with estimates of genetic potential. There is a significant, positive correlation of MFP$ (economic index for milk traits) of a bull with the area under the GH response curve (AUC-GH) upon GHRH challenge (19,20). Similarly, sheep selected for fatness over lean have a lower AUC-GH than those selected for lean gain (34).
Accretion of body mass, i.e. growth, is essential to the production of red meat. GH in turn, is critical to normal animal growth. In addition, GH is necessary for normal lactation in ruminants. For these reasons a great deal of research has focused on understanding GH secretion and actions, and has led to the use of exogenous GH, or its secretagogue GHRH, to enhance the efficiency of animal production. Elevation of circulating GH can markedly reduce fat accretion which increases the desirability of meat products by an increasingly health conscious public.
An understanding of the central nervous control of GH secretion as provided by the present invention results in new methods to select for animals superior in endogenous GH secretion, and therefore increase the production efficiency and consumer acceptability of animal products. Because of its role in ruminant growth and lactation, variation in GH secretion may provide a tool to assess an animals potential for meat or milk production. Secretion patterns of GH including peak frequency and peak duration are related to dairy merit; however, mean serum GH is not related to dairy merit (Klindt, 1988; Kazmer et al., 1990, 1991). Purchas et al. (1970) found no relationship between basal GH and growth performance of cattle and no relationship has been demonstrated between GH pulse characteristics and growth of lambs (Klindt et al., 1985) nor cattle (Ohlson et al., 1981). Conversely, sheep and cattle selected for rapid gain exhibit higher plasma GH concentrations than unselected lines (Dodson et al., 1983; Ohlson et al., 1987).
In contrast, pituitary gland responsiveness to GHRH is a reliable indicator of dairy merit and provides more consistent results than spontaneous serum GH measurement (Lovendahl et al., 1991; Zinn et al, 1994). Further, studies of fat and lean sheep (Suttie et al., 1991) suggest that responsiveness to GHRH is predictive of composition of gain. The objective of the present study was to deter
Barao Scott M.
Connor Erin E.
Dahl Geoffrey E.
Le Long V.
Padmanabhan Kartic
University of Maryland College Park
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