Decuypere, E.
Bruggeman, V.
Buyse, J.
Lab of Physiology of Domestic Animals,
B-Leuven, Belgium
The present paper gives an overview of the role of the hypothalamo-pituitary-adrenal (HPA) axis in the response upon stress in poultry. The secretion of corticosterone, the major adrenal glucocorticoid is regulated by a whole array of factors (mainly ACTH and prolactin) and exerts long- and short-loop feedbacks on its own secretion. The physiological consequences of the activation of the HPA axis as well as the interaction of the HPA axis with other hormonal axes (somatotrophic, thyrotrophic and gonadal axes) are discussed.
The HPA axis is also involved in the regulation of voluntary feed intake, probably by interacting with leptin and neuropeptide Y. Not only the absolute amount of feed uptake but also the self-selection of dies based on their macronutrient contents, is influenced by the HPA axis. Finally, the impact of nutritional aspects (quantity as well as quality) on the activation of the HPA axis is documented.
Introduction
The notion of "adaptation" in the common sense and not in its genetic or evolutionary context is linked with welfare since exhaustion of the possibilities of adapting to adverse situations will result in stress and hence lack of welfare and possibly in a pathogenesis for the animal.
This adaptation response of the animal has a physiological component, related to the theory of stress and a psychological component related to coping. In this overview we mainly deal with stress-physiology that is the study of disturbances of the physiological balance and of the mechanisms that restore this balance, mainly the activation of the hypothalamo-pituitary-adrenal (HPA) axis and of the orthosympathic nervous system (ANS).
The paired adrenals in poultry are located close to the cephalic lobe of both kidneys. In contrast with mammalian species, no clear distinction can be made between cortex and medulla in avian species. The chromaffin cells (CC) are located in clusters in between the adrenocortical cells (AC).
Based on localization, cytochemical or ultrastructural studies, two chromaffin cell types exist containing either norepinephrine (NE) or epinephrine (E) and two adrenocortical cell types secrete either aldosterone or corticosterone (B), the latter being the predominant glucocorticoid in birds whereas this is cortisol in most mammalian species (Carsia and Harvey, 2000). Corticosterone secretion is mainly ACTH-dependent although a large number of other factors, hypophysical as well as peripheral, are also modulating corticosterone secretion by adrenal AC-cells as reviewed by Carsia and Harvey (2000); prolactin in birds is one of the most prominent factors amongst those that stimulate corticosterone secretion (Figure 1).
Corticosterone in blood is largely bound to a specific binding protein, transcortin (high affinity, low capacity) and a-specifically to albumin. This binding results in a stabilisation of free hormone in circulation by decreasing elimination at the level of kidney and liver.
Feedback regulation of corticosterone is present at all levels of the HPA-axis, and free/bound ratio is controlled by the stimulating effect of B and inhibitory effect of thyroxine, testosterone as well as low protein-diets on circulating transcortin levels.
The sensitivity of the hypothalamo-pituitary axis for B-feedback can be altered by some of these modulations factors, e.g. prolactin decreases the short-loop feedback of B on its own secretion.
The close association between AC and CC cells in avian adrenal glands give rise to a large number of paracrine interactions as reviewed by Carsia and Harvey (2000), hence to a mutual HPA-ANS interaction.
The physiological stress response consisting in activation of the HPA-axis and the ANS has a cost: it results in decreased appetite, anabolic processes, gastrointestinal activity, reproductive capacity, immune function, inflammation and pain reaction, and in increased respiratory and cardiovascular tonus, blood pressure and heart frequency, blood volume and water retention. The redistribution of blood volume is based on increasing epinephrinergic and decreasing cholonergic activity of the ANS.
The endocrine changes involved in these decreases of production-related physiological functions will be further documented in the next paragraph in relation to the activation of the HPA and orthosympathic ANS. In a last paragraph, nutritional stress and the impact of stress on nutrition in poultry will be documented.
Interaction of the HPA-axis with other endocrine axes
In general, glucocorticoids in mammals and birds (poultry) are inhibiting growth as a result of increased muscle protein catabolism. Simultaneously fat deposition, mainly abdominal fat, is increased as a result of stimulated lipogenesis and reduced lipolysis.
Corticosteroids inhibit the hormone sensitive lipase (HSL) and hence could inhibit the antilipolytic effect of insulin, but stimulate the lipoprotein lipase (LPL), blood triglycerides, and fat deposition. In the chicken, exogenous corticosterone increases glycogenolysis and hyperglycaemia (Simon, 1984) together with plasma levels of insulin and hence induces insulin-resistance (Taouis et al., 1993). GH and testosterone are counteracting these effects of corticosteroids, but increased corticosterone levels are decreasing circulating levels of GH, IGF-I as well as T3 levels. Corticosteroids are inhibiting the thyroid axis at all levels, including peripheral conversion of T4 into its active compound T3 and expression of nuclear T3-receptors (in mammals). This may result in an energy-sparing effect during stress resulting in a decreased heat production that is not linked with physical exercise. Intensive physical training as well as anorexia or fasting are coupled with decreased thyroid functioning and increased glucocorticoid levels. Moreover a multilevel interaction between the thyrotrophic and somatotrophic axis in chickens is documented elsewhere (Kühn et al., 1991).
Chronic stress and increased levels of corticosteroids have a rather complicated and unequivocal effect upon endocrine control of reproduction; these effects are species- and sometimes season- dependent as well as on the duration and intensity of the stressor. The temporal synergism between corticosterone and prolactin in premigratory hyperphagia and subsequent fat deposition and gonadal functioning as well as between corticosterone and LH during the breeding season are described for several avian species.
This breeding-associated increase in B is due to a reduced B-negative feedback on the HPA-axis and enhanced responsiveness of the adrenal to ACTH.
On the other hand, induced molting in hens reduces the entire HP-gonadal axis while plasma corticosterone levels are increased. An acute increase of HPA-Activity however seems to be able to induce a preovulatory LH surge (Sharp and Beuving, 1978) and ovulation (Ethes and Cunningham, 1976).
Therefore, in poultry as in domestic mammals, the general rule that chronic stress is inhibitory while acute stress is mostly stimulatory upon reproductive performance may hold true. This opposite reaction is due to the many interactions of stress signals upon the hypothalamo-pituitary-gonadal axis, but with different impact according to time and duration of the stressor.
The stress-response and immunosuppression as well as analgesia are well documented in mammals but to a much lesser extend in poultry (for review, see Glick (2000) and Carsia and Harvey (2000) and will not be discussed here.
Stress and nutrition and nutritional stress
Interaction HPA-axis and food intake
In the complex control of food intake regulation in mammals, hypothalamic factors Corticotrophin-Releasing Factor (CRF) and Neuropeptide Y (NPY), and peripheral factors insulin, cortisol and leptin interact with each other in a complex way. The potent orexigenic peptide NPY is stimulated by cortisol and inhibited by insulin and leptin.
Corticosterone increases and centrally administered CRF decreases feed intake also in the chicken. Since dexamethasone induces leptin secretion by the liver of the chicken, the corticosterone-induced hyperphagia may be mediated by interaction of leptin on CRF and NPY-gene expression in the hypothalamus, as also found in the rat model.
Stress also induces secretion of catecholamines, which have been shown to increase food uptake in broilers when administrated centrally, but not in layers.
A number of other secretory products by the CC cells of adrenal glands have been described (serotonine, galanine, somatostatine, cholecystokinin, NPY) but to what extend these substances are acting as endocrine factors reaching the hypothalamic appetite/society centers through the blood-brain barrier, is not known, at least not in avian species.
Corticosterone and food choice
Experimental evidence with choice feeding experiments using feeds with different protein content indicates that broilers as well as laying hens can make an optimal choice in order to fulfill their requirements for growth or egg production, respectively. Regulation for energy uptake is not as finely tuned and certainly not in broilers.
However, stressful conditions that mobilize chronically the HPA-axis may interfere with this food choice. Adding corticosterone to the feed of broilers (60 ppm) increased the proportional intake of high protein diet (HP: 28 % CP versus 7 % CP for LP), while total protein uptake increased, fat deposition increased and protein accretion decreased.
In an experiment, Malheiros et al found that addition of corticosterone significantly changed the diet selection of broilers that were allowed to chose freely for 14 days between three isocaloric diets in which only one macronutrient (protein, lipid, carbohydrate) was isocalorically substituted for one other macronutrient. The consumption of the low protein diet increased whereas the consumption of the low fat diet decreased. Furthermore, corticosterone-supplemented chickens were characterised by hyperglycemia, hyperlipidemia and elevated plasma uric acid levels, indicative for insulin resistance and protein catabolism, respectively. Plasma creatine kinase activity was increased manifold, suggesting a direct effect of corticosterone on muscle cell membrane integrity. The major driving force of these altered food preferences in a state of hypercorticosteronemia probably is the changed intermediary metabolism although changed taste preferences, or other higher order (brain) induced changes as a consequence of the chronic high circulating corticosterone levels cannot be excluded.
Quantitative feed restriction
Restricted feeding, as is common practice in broiler breeder raising, as well as fasting hens leads to increased plasma corticosterone levels and elevated heterophyl/lymfocyte ratios (as a consequence of the former), indicating a chronic stress condition. The whole endocrine system involved in the control of intermediary metabolism is concomitantly changed in a homeorhetic shift from anabolism to catabolism, lipogenesis to lipolysis and towards energy-sparing mechanisms (Buyse et al., 2000). This is also reflected in changes in plasma concentrations of key metabolites (Buyse et al., in press).
In terms of animal welfare, artificial molt of laying hens by fasting or severally restricting the birds for a rather long period (several days to weeks) is under pressure from different society groups as well as from the legislator. Autonomous feed restriction by diluting diets (oat pellets) or adding specific compounds such as jojoba-meal in a well-defined proportion (based on the content of its anorectic substance simmondsin) normalized the plasma corticosterone levels, indicating that it is the stress of the absence or shortage of food per se and not primarily the available metabolisable energy or protein within the animal that increased corticosterone levels.
Qualitative feed changes and the HPA axis
Low protein diets are the most studied qualitative feed changes, and can be considered as a "metabolic" stress to which the birds have to adapt their metabolism.
As with feed restriction, GH levels increased and IGF-I decreased, but T3-levels increased with low protein diet whereas fasting or feed restriction invariably decreases plasma T3 levels. This can be understood in a teleological way since feed restriction will activate energy-sparing mechanisms, including a decreased metabolic level per unit body weight that is related to a lower T3 level.
Moderate protein restriction on the other hand will relatively increase food intake to compensate for protein and essential amino acid requirements, hence will result in overconsumption of energy. This 'luxus' energy consumption is dealt with in two ways: partly deposited as excess fat as well as turned into heat production, the latter phenomenon brought about by the increased T3 levels.
References
Buyse, J.; Decuypere, E.; Darras, V.M.; Vleurick, L.M.; Kühn, E.R. and J.D. Veldhuis. 2000. Food deprivation and feeding of broiler chickens is associated with rapid and interdependent changes in the somatotrophic and thyrotrophic axis. British Poultry Science 41: 107-116.
Buyse, J.; Janssens, K.; Van der Geyten, S.; Van As, P.; Decuypere, E. and V.M. Darras. Pre-and postprandial changes in plasma hormone and metabolite levels and hepatic deiodinase activities in meal-fed broiler chickens. British Journal of Nutrition, in press.
Carsia, R.V. and S. Harvey. 2000. Adrenals. In: Sturkie's Avian Physiology, Fifth Edition (Ed. G.C. Whittow). Academic Press, San Diego London. pp. 489-537.
Ethes, R.J. and F.J. Cunningham. 1976. The effect of pregnenolone, progesterone, deoxycorticosterone or costicosterone on the time of ovulation and oviposition in the hen. British Poultry Science 17: 637-642.
Glick, B. 2000. Immunophysiology. In: Sturkie's Avian Physiology, Fifth Edition (Ed. G.C. Whittow). Academic Press, San Diego London. pp. 657-670.
Kühn, E.R.; Herremans, M.; Dewil, E.; Vanderpooten, A.; Rudas, P.; Bartha, T.; Verheyen, G.; Berghman, L. And E. Decuypere. 1991. Thyrotropin-releasing hormone (TRH) is not thyrotropic but somatotropic in fed and starved adult chickens. Reproduction, Nutrition and Development 31: 431-439.
Malheiros, R.D.; Moraes, V.M.B.; Collin, A.; Decuypere, E. and J. Buyse. Free diet selection by broilers as influenced by dietary macronutrient ratio and corticosterone supplementation. 1. Diet selection, organ weights and plasma metabolites. Poultry Science, in press.
Sharp, P.J. and G. Beuving. 1976. The role of corticosterone in the ovulatory cycle of the hen. Journal of Endocrinology 78: 195-200.
Simon, J. 1984. Effects of daily corticosterone injections upon plasma glucose, insulin, uric acid and electrolytes and food intake pattern in the chicken. Diabete Metabolism 10: 211-217.
Taouis, M.; Derouet, M.; Chevalier, B. and J. Simon. 1993. Corticosterone effect on insulin receptor number and kinase activity in chicken liver and muscle. General and Comparative Endocrinology 89: 167-175.
