Cortisol, production and robustness
Cortisol and production traits
Cortisol has complex, and mostly negative, effects on production traits. Hennessy et al. (1988) showed that the adrenal response to ACTH in pigs is an individual trait and that growth rate and feed efficiency are negatively related to the intensity of this response (Hennessy and Jackson, 1987). Similar results have been obtained in sheep, with residual feed intake being directly proportional to the release of cortisol after injection of ACTH (Knott et al., 2008). An extensive study of the effects of corticosterone in chickens chronically infused with ACTH describes the effects of adrenal stimulation on production (e.g. reduced feed intake, body and carcass weight) and physiological (e.g. increased liver weight and lipid content, increased adrenal glands weight and plasma concentrations of glucose and lipids) traits (Puvadolpirod and Thaxton, 2000a, 2000b, 2000c and 2000d; Thaxton and Puvadolpirod, 2000). In pigs, several examples show that leanness is influenced by the cortisol production rate as measured, for instance, by the excretion level in urine (Foury et al., 2005 and 2007). All these changes result mainly from the physiological effects of GR hormones on metabolism, with an increase of energy storage (fat and glycogen) at the expense of tissue proteins (Devenport et al., 1989).
Cortisol and robustness
By contrast, several lines of evidence show that cortisol has positive effects on robustness traits, although experimental data are still fragmentary, especially in farm animal species. GR hormones strengthen adaptation processes. Michel et al. (2007b) studied individual variations in responses to heat stress in rats. The animals with the strongest HPA axis response, as measured by the circulating corticosterone levels, displayed a more efficient physiological adaptation to the heat stimulus, with a lower increase of core temperature and haemoconcentration, and a reduced inflammatory response in the brain. These differences reflect the physiological effects of GR hormones (Michel et al., 2007a) and show that the animals that mount a strong stress response adapt better to the stressor. The generalization of these results to other stress stimuli is still to be demonstrated.
Another example of the positive influence of stress hormones on robustness traits can be found in the work on newborn piglet survival by Leenhouwers et al. (2002), who showed that piglet viability is a heritable and piglet-intrinsic trait. The only biological characteristics correlated (positively) with the estimated breeding value for piglet survival were the size of the adrenal glands and the concentration of cortisol in cord blood collected at birth. These endocrine measurements were also correlated positively with the relative weight of the small intestine and higher concentrations of glycogen in liver and muscle that reflects the gluconeogenetic properties of cortisol (Mayor and Cuezva, 1985). Indeed, during the final days of gestation, there is a surge of HPA axis activity in the foetus (Silver and Fowden, 1989; Kattesh et al., 1990; Heo et al., 2003) that mediates, together with insulin, liver glycogen accumulation during the late foetal stage (Bollen et al., 1998). Large differences in metabolic traits have been described among pig breeds (Hoffman et al., 1983), suggesting a role of genetic factors. This mechanism may at least partly explain the exceptional viability of Meishan piglets (Canario et al., 2009), as this breed displays a high activity of the HPA axis (Klemcke and Christenson, 1997; Désautés et al., 1999).
Finally, experimental evidence in poultry shows that genetic selection for the intensity of the HPA axis stress response has a complex influence on immune responses and resistance to diseases. For instance, chickens from a line selected for high levels of plasma corticosterone when housed in an environment facilitating considerable social interaction were more resistant to parasitic infestation by Eimeria necatrix than those from a line selected for low levels of plasma corticosterone housed in an environment that minimized social interaction (Gross, 1976). Recently, Minozzi et al. (2008) showed that genetic selection of Leghorn chickens for different immune traits did not modify corticosterone response to stress or to ACTH, but within lines, several immune traits were correlated with the level of several immune parameters. It is worth noting, for instance, that in the line selected for high antibody response to Newcastle disease virus, vaccine basal corticosterone concentrations were negatively correlated to phagocytic activity measured by carbon clearance, but stress corticosterone response was positively correlated with the antibody response (Minozzi et al., 2008). These differences reflect the complex effects of corticosteroid hormones on the immune system and inflammatory processes (Salak-Johnson and McGlone, 2007; Marketon and Glaser, 2008).
Altogether, these data suggest that GRs have a positive influence on several robustness-related traits. Considering the above-mentioned general development towards less supportive production conditions, this positive influence is worth being explored in more detail.
Cortisol: trade-off factor between production and robustness
It is common sense that robustness and production levels do not go along together very well. Local breeds, well adapted to their (eventually harsh) environment have usually low absolute levels of production, although it may be high considering the environmental constraints. By contrast, genetically selected, highly productive stocks frequently show signs of reduced robustness (Rauw et al., 1998; Star et al., 2008; Knap and Rauw, 2009; Siegel et al., 2009; Veerkamp et al., 2009). This trade-off between productivity and robustness is predicted by the resource allocation theory (Beilharz, 1998; Glazier, 2009) – the energetic resources of an individual are limited and their allocation across metabolic functions is optimized towards the best adaptation of the individual to its environment ( = fitness). Genetic selection for production traits logically redirects resources towards those production traits, at the expense of other traits (such as robustness traits). When resources are not sufficient to support full expression of the production potential, this becomes problematic, and leads to genotype × environment interaction.
The HPA axis is primarily a neuroendocrine system involved in numerous physiological regulations. Its implication in stress responses results from its ability to mobilize energy to support adaptation, but this catabolic activity is exerted at the expense of anabolism-based production potential. Therefore, the effects of cortisol on production and robustness traits as described in the previous paragraphs are two facets of the role of the HPA axis in homeostasis and adaptation, but it appears that these effects of cortisol may be antagonistic. Recently, in the French Large White pig breed, a comparison of progeny from sires born in 1977 (frozen semen) v. 1998 to 2000 (Foury et al., 2009) showed a decrease of the production of cortisol (urinary cortisol at slaughter), together with an improvement of production traits (growth rate, feed efficiency, leanness). This trend illustrates the above-mentioned negative effect of cortisol on production traits, so that HPA axis activity was counter selected in the selection process for production traits. As a consequence, this decrease in HPA axis activity may explain part of the compromised robustness that coincides with over-focused genetic improvement of production traits in farm animals.
Therefore, the HPA axis appears as a putative physiological element of the trade-off between production and robustness traits, which cortisol influences negatively and positively, respectively. Hence, an additional strategy to those listed above to increase farm animal robustness would be to strengthen the HPA axis activity, but without the possible side effect of increased cortisol production to compromise productivity. This objective does not appear to be out of reach. Indeed, the functional variability of the HPA axis is usually very large, even in genetically homogeneous populations. Foury et al. (2007) found a 30-fold range of urine cortisol concentrations in each of five pure pig lines, much more than the variation of production traits. In the above-mentioned study of genetic trends of stress-responsive systems in the French Large White, (Foury et al., 2009) found a −0.27 correlation between cortisol levels (in urine collected from the bladder after slaughter) and carcass lean content, so that only 0.27 × 0.27 = 7.3% of the variance of leanness is related to differences in cortisol production. It is therefore possible to envisage the selection for a stronger HPA axis to improve robustness without compromising production traits. Indeed, it was previously shown that the introduction of ‘functional traits’ in selection programmes could efficiently improve robustness without compromising the genetic gain on production traits (Knap, 2009).