Effects of stress hormones on digestibility and performance in cattle: A review

Abbreviations

ACTH

adrenocorticotropic hormone

AMP

adenosine monophosphate

BAX

apoptosis regulator BAX (bcl-2-like protein 4)

BCL2

B-cell lymphoma 2

BCS

body condition score

DCAD

dietary cation–anion difference

DMI

dry matter intake

CA

catecholamine

CK

creatine kinase

GC

glucocorticoids

GDF15

growth differentiation factor 15

HPA

hypothalamic–pituitary–adrenal

HS

heat stress

IGF1

insulin growth factor type 1

LDH

lactate dehydrogenase

NEB

net energy balance

WHC

water holding capacity

1 Introduction

A stress response is a reaction to environmental conditions that cause undesirable and harmful consequences [1,2]. In other words, stress is a non-specific reaction that occurs under the influence of external and internal stressors [3,4]. Various stressors affect organismal biology, such as the endocrine system, which impacts cattle’s physiology [5]. The environmental stressors include heat, cold, wind, and humidity [6], nutrition (feeds and feeding methods), endocrine disruptors [7,8], and management (housing and hygiene, transportation, and weaning process) [9,10]. As cattle pass through their production cycle, they are exposed to a range of stresses that make them more likely to become ill.

The hormones produced by stressful situations affect the function and distribution of immune cells throughout the body, and they have a variety of detrimental impacts on organisms’ health. Furthermore, animals’ movement causes a variety of physical, psychological, and environmental stresses, depending on how and for how long they move [11]. Therefore, transfer stress (at slaughter time) can affect meat quality [12]. In addition, stress can alter pituitary hormone release, which may affect metabolic function, immunological competence, and behavior [13,14]. A wide range of stressful events induce an increase in circulating glucocorticoids (GCs) through the hypothalamic–pituitary–adrenal (HPA) axis. GC hormones have anti-inflammatory, metabolic, and vasomotor functions that assist the body in dealing with life-threatening situations [15]. The original name of growth differentiation factor 15 (GDF15), was macrophage inhibitory cytokine-1 [16]. GDF15 is a hormone that is produced by a number of cells when they experience stress. As a result of binding to a brain receptor, macrophages transmit negative messages to the body. By activating the endocrine stress response, primary GCs (stress steroids) are released into the bloodstream [17].

The most significant threat to dairy cow production is heat stress (HS), which is mediated by complex molecular systems and produces a wide range of biological and hormonal responses [18]. Aside from stimulating the sympathetic–adrenomedullary axis, HS also stimulates the adrenal medulla to secrete catecholamines (CAs) such as norepinephrine, epinephrine, and dopamine [19–21]. In addition to maintaining a constant internal environment, GC and CA allow the body to regulate metabolic activity and reduce HS response. Inhibition of the hypothalamic–pituitary–gonadal axis by adrenocorticotropic hormone (ACTH) and GC can negatively affect hypothalamic hormone secretion, thereby reducing gonadotropin-releasing hormones, follicular stimulating hormones, estrogens, progesterone, and testosterone production. In animals, a higher level of insulin may result in an increase in prolactin, which may result in lower reproductive performance [22]. In HS, ACTH is important for thermoregulation and metabolic adaptation [23]. There is no known mechanism by which stress hormones work, but it has been suggested that cortisol converts glycogen into energy, thereby aiding in the mobilization of energy reserves during acute or chronic stress. Stress, however, causes cortisol levels to rise and muscles to deplete glycogen stores. By mobilizing energy under short-term stress, GCs promote fitness as well as alter behavior such as ruminating [24].

Consequently, stress hormones play a key role in animal production, welfare problems, and animal biology. Therefore, the authors see value in compiling and discussing the novel findings in the area of stress hormones in cattle. This study was hence divided into four sections (feed digestibility, milk production, milk composition, and meat quality) in order to better review how stress hormones affect cows’ feed digestibility and overall performance.

2 Effect of stress hormones on feed digestibility

Increased levels of cortisol caused by chronic stress in ruminants alter most physiological processes [25]. Typically, high cortisol suppresses the immune system, redirects energy away from growth and digestion, and elevates protein breakdown, which therefore affects the efficiency of nutrient use [26]. According to Xu et al. [27] the digestive process of ruminants relies mostly upon symbiosis with gut microbiota for degrading cellulose like complex feed components. Therefore, chronic stress can cause an imbalance in the gut microbiota, which in turn negatively affects fermentation efficiency in the rumen [28]. Reduced microbial activity impairs the degradation of fiber components and consequently the total digestibility of feed [29].

Moreover, stress hormones can decrease the secretion of digestive enzymes and modify gut motility, further impairing digestion [30]. According to Smits et al. [31] reduced feed digestibility contributes to ingested nutrients not being optimally absorbed, thereby resulting in poor growth rates and associated lower milk production in dairy animals. The inefficiency imposes higher feed intake to meet nutritional requirements, increasing feeding costs.

The transition period (the 3 weeks before calving and the 3 weeks following calving) has been reported to be challenging for dairy cows, resulting in shortages of energy and nutrients, inflammation, increased lipid peroxidation, hormonal and metabolic changes [32,33]. Added anionic salts to pre-calving diets could stabilize Ca homeostasis and postpartum performance; however, it has been argued that this could negatively affect prepartum intake [32,34]. When the dietary cation–anion difference (DCAD) of prepartum cows is reduced by 300 mEq/kg (milliequivalents per kilogram), the dry matter intake (DMI) decreases by 1.3 kg/day [35]. A negative-DCAD diet has been used by dairy producers for several years to prevent milk fever and subclinical hypocalcemia [36]. There is some evidence that anionic sources’ low palatability may be contributing to the reduction of prepartum consumption [32,37]. As a result of anionic salt supplementation in pre-calving meals, several meta-analyses indicate that this can result in compensated metabolic acidosis that boosts tissue parathyroid hormone responses, reducing the likelihood of hypocalcemia [34]. These studies also found that low DCAD diets increased milk production and postpartum intake, but reduced prepartum intake. The blood Ca²⁺ levels and low DCAD ratios could also affect DMI [33].

When thermal stress occurs, the HPA axis releases GCs and aldosterone [38]. As cattle adapt to high thermal stress, norepinephrine, epinephrine, and cortisol levels tend to increase in the bloodstream, whereas aldosterone levels tend to decrease due to increased K⁺ loss because of sweating [25]. These types of hormonal changes reduce the levels of thyroxine and triiodothyronine in plasma as well as the basal metabolic rate, resulting in a decrease in heat production [39]. Due to high IGF-II levels and low circulatory levels of somatotrophins, significant changes in dietary intake were also observed under HS [25].

Animal nutritionists agree that nutrition is crucial for the calf and heifer during both pregnancy and growth. In fetal development, for example, the metabolic environment may lead to epigenetic changes that further affect the reproductive potential of heifers [40]. Insufficient or imbalanced nutrition can negatively impact post-calving estrus cyclicity by reducing the net energy balance (NEB). According to Ginther [41] NEB inhibits insulin growth factor type 1 (IGF1) release, leading to an immature oocyte before ovulation. In addition, D’Occhio et al. [42] reported that beef heifers have higher body condition scores (BCS) primarily due to increased levels of IGF1, and this hormone accelerates puberty onset and decreases postpartum anestrus in conjunction with other hormones like leptin and ghrelin. Fernandez-Novo et al. [43] recommended 2.5–3.0 of BCS to maintain energy balance and promote reproduction.

Slow-release stress hormones are important to appreciate in ruminant health and productivity [44]. Effective strategies of management of stress can be employed to enhance feed efficiency, better growth performance, and generally improved welfare of such animals, hence more sustainable and economically viable productions in livestock [45].

3 Effect of stress hormones on milk production

Different biological factors play a role in the development of the mammary gland, including peptide hormones, steroid hormones, extracellular factors, and local factors [46]. In the mammary gland, corticoids act on specific receptors known as GC receptors, which produce milk. In the presence of these receptors, corticoids generate a specific physiological response [47]. Cortisol affects arteriovenous pressure, which is essential for milk production [48], but other stress hormones, such as ACTH , decrease milk yield. Similarly, other researchers also reported that cortisol is essential for milk production [49]. Moreover, it was found that chronic stress leads to an increase in cortisol levels, while acute stress results in a decrease in cortisol levels [50]. Tao et al. [51] and other researchers demonstrated that under stressful conditions, cortisol levels are elevated, stimulating proteins such as B-cell lymphoma 2 (BCL2) that stop the apoptosis process and allow mammary gland epithelial cells to survive. Nonetheless, stress, specifically acute stress, causes cortisol hormone release and decreases milk production [52]. In their research, Chen et al. [53] also found that acute stress increases cortisol levels, but they return to the basal level after 4–6 h. In the same way, it was found that cortisol also stimulated BAX gene expression (apoptosis regulator BAX, also known as bcl-2-like protein 4), which initiated the pro-apoptotic process without affecting BCL2 and led to apoptosis [54]. Due to these responses, cortisol’s effect on milk production and epithelial cell survival is complex, and further research is required [48].

Acute and chronic forms of stress have a very potential effect on milk yield and quality. Specific effects can be found on production parameters of milk including milk volume, fat content, protein concentration, and somatic cell count [55]. A change in the environment is one example of acute stress, which results in a peak increase in cortisol levels [50]. This peak disrupts metabolic activity and thus milk yield is lowered for a short period. Acute stress also influences milk composition, as it lowers the contents of fat and protein and increases that of somatic cell count (SCC), which reflects poorer milk quality [56]. Salama et al. [57] demonstrated that acute stress events can reduce daily milk yield by up to 21% and dramatically affect milk composition, even within a few hours surrounding the stressor.

Chronic stress is a response to continual and prolonged exposure to some aversive condition, for example, poor housing, inadequate nutrition, or constant high temperatures [58]. This type of stress has more deep-rooted and long-lasting effects on milk production, lowering yield and having a great effect on its composition, such as lower fat and protein percentages, higher SCC indicative of increased mastitis risk. According to Habimana et al. [59], milk yield can be decreased by approximately 15–20% under chronic stress conditions during a longer period of exposure and significantly affects the nutritional and hygienic quality of milk.

Apart from cortisol, other hormones released as the products of stress, for example, adrenaline and noradrenaline play a role in milk production [61]. As has been well documented, these stress-related hormones decrease blood flow to the mammary gland and lower milk synthesis and ejection by stimulating peripheral vasoconstriction [62]. Higher levels of these hormones (adrenaline and noradrenaline) at the time of the stress event reduce milk letdown at milking and thus make their milking incomplete, and milk yields are thus reduced [63]. Cortisol’s effects on milk production and epithelial cell survival are multifaceted and complex [64]. Cortisol may help the body deal with stress at the outset, but sustained exposures result in apoptosis of the mammary epithelial cells, impairing milk production by the mammary gland [65].

According to Matamala et al. [66] appropriate practice in handling and housing of cows can lessen stress through adequate space, comfortable bedding, and stability in the environment a place that is not stressful. Koenneker et al. [67] suggested that training low-stress animal handling techniques for farm personnel will help in reducing acute stress during milking and other procedures. Environmental control: improvement in ventilation and temperature regulation helps the animal to alleviate common chronic stressors like HS in dairy cows [68]. Second, a balanced diet fulfilling all nutritional requirements aids the cows in coping with stress [25]. Vitamin and mineral supplementation, which is known to speed up stress resilience, such as vitamin E and selenium, can lead to overall better health status and milk yield [69].

4 Effect of stress on milk composition

Stress conditions also negatively affect milk composition [70]. According to Bouraoui et al. [71], HS negatively impacts milk composition as well. Also, animals become more sensitive to HS as their milk production increases. This may be caused by an increase in metabolic activity [72]. Figure 1a summarizes the effect of HS on milk parameters, i.e., production quantity and quality. The content of milk fat and protein was found to be reduced at high temperatures (summer season) whereas lactose content did not increase [73]. It has been reported that HS alters the hormonal level of milking animals [74]. According to Helal et al. [75], an increase in temperature decreases thyroid hormone production. Due to this, the metabolism of animals slows down, causing the drop in milk production [74]. Aside from altering animal digestion, HS also causes decreased acetate production, increased butyrate and propionate production, and changes in milk composition [76]. Other researchers suggest that HS has a negative impact on milk yield and composition, and that high-producing animals experience the most significant effects [77].

Figure 1

Effect of stressors on the quality of milk (a) and meat (b). Source: [59,60].

Numerous research investigations have indicated a correlation between HS and reductions in overall protein and fat levels. Nevertheless, certain researchers have reported no substantial decrease in fat content among cows experiencing HS [71,78–81]. Bouraoui et al. [71] observed a decrease in milk fat and milk protein levels during the summer season. In a separate study, Ozrenk and Inci [82] noted that cow milk exhibited the highest concentrations of fat, protein, and total solids in the winter months, with the lowest levels recorded during the summer. HS has been found to decrease milk protein, milk fat, and solids-not-fat in dairy cows. Additionally, HS has been shown to lower milk fat, protein, and short-chain fatty acid levels, while increasing the concentration of long-chain fatty acids in milk [83,84]. Another study reported reduced levels of milk protein, lactose, and fat during the summer months [60,85]. The decrease in protein concentration during HS may be linked to the specific downregulation of mammary protein synthesis as part of thermoregulatory processes [86]. Moreover, an increase in the heat load index has been associated with a decline in lactose, protein, and fat concentrations in milk [87].

In ruminants stress also affects milk composition, influencing variation in fat, protein, lactose, and other components [88]. Various stages of lactation may show an enhanced response to stressors that may further affect milk composition. According to Eslamizad et al. [89], a low milk fat percentage resulted from chronic stress exposure in cows, which is attributed to disruption in lipid metabolism and a reduction in feed intake. The period of early lactation is particularly risky for stress impacts because at this point in the lactation cycle, energy demands are so high for cows, and these would get even more enhanced by stress, resulting in a negative energy balance that would have negative effects on fat synthesis in the mammary gland [90].

According to Sejian et al. [69], chronic stress resulted in a decrease in milk protein percentage in cows. The reduction is attributed to amino acids being diverted from milk protein synthesis to other metabolic processes needed to cope with stress. The reason for this is that early lactation cows are already under metabolic stress, so the supplementary stressors may cause a more pronounced depression in milk protein content [91]. Acetate, butyrate, and propionate represent volatile fatty acids (VFAs) coming from rumen fermentation and act as important milk component precursors [92]. Acetate is the major precursor of milk fat, while propionate represents the key glucose precursor and hence influences lactose synthesis; butyrate acts as a supporter of the general energy supply and milk fat synthesis [93]. According to Liu et al. [94] stress can alter the rumen microbial balance and decrease the production of these VFAs. Stressed cows exhibit less acetate concentration in the rumen, a situation which decreases milk fat content [88]. Similarly, low propionate production because of stress will also restrict lactose synthesis, producing effects on milk volume and quality [95].

5 Effect of stress hormones on meat quality

A wide range of meat quality parameters are used to assess meat quality, including its compositional quality and palatability [96], as well as its appearance, juiciness, tenderness, and flavor. According to Geletu et al. [97], the color of meat can be affected by the amount of myoglobin in the muscle, whereas the juiciness, tenderness, and flavor of meat are greatly affected by intramuscular fat (marbling). Research has revealed that uniform meat coloring, marbling, and water holding capacity (WHC) are strongly correlated with consumer preferences [98,99]. It is undeniable that the slaughter process is a critical step in the production of meat from live animals for human consumption. Several stressor events occur during slaughtering because of physical, psychological, or behavioral factors, causing fatigue, hunger, pain, thermal, and respiratory discomfort [100,101]. In Figure 1b, the authors summarize the impact of stressors on meat quality. As cortisol and CA levels increase in the abattoir, it becomes more difficult to handle stressed cattle [102]. In addition, behavioral reactions following physiological changes might negatively affect meat quality. In stressful slaughtering conditions, muscle glycogen content can be reduced, resulting in higher meat pH and a low residual glucose content [103]. Additionally, Honikel [104] found that pre-slaughtering stress factors can negatively impact muscle biochemistry and physiology after death. To better understand the effect of pre-slaughter handling and transport on livestock stress levels [105,106], previous studies examined plasma concentrations of stress hormones (e.g., CA and cortisol) as well as biochemical (e.g., glucose, creatine kinase [CK], and lactate dehydrogenase [(LDH]) and hematological variables. According to Rutherford et al. [107], CK and LDH are two of the most detected muscle enzymes in serum following muscular damage. Conversely, cortisol is secreted because of ACTH release and can be detected in serum within a few minutes of exposure. The adrenaline hormone is also crucial when determining meat quality [108]. According to previous research, a higher heart rate before slaughtering positively correlates with meat pH [102]. As a result of adrenaline’s stimulatory effect on adenosine monophosphate (AMP) deamination, several researchers have connected higher AMP deaminase activity with higher meat pH due to higher heart rate which is associated with higher adrenaline level [102,109]. Previously, it has been shown that muscle fiber type proportions heavily influence muscle metabolism [110]. According to Beline et al. [111], muscle hypertrophy and the ratio of fast-glycolytic Type-IIB myofibers (skeletal muscle fibers) increase with muscle selection, whereas the percentage of slow-oxidative Type-I myofibers decreases. It is thus expected that the ability to produce glycogen and glycogenolytic products will increase for cattle selected for muscling as glycogen phosphorylase activity is higher while glycogen synthase and hexokinase activity is lower. As well as increasing glycolytic and glycogenolytic capacity, stress (adrenaline) can lead to glycogen depletion, along with a decreased ability to resynthesize glycogen; this reduces muscle glycogen at slaughtering and increases the likelihood of dark, firm, and dry (DFD) meat [112]. Fasting for up to 12 h seems not to cause livestock any physical discomfort. The fasting period, however, increases reactivity to certain slaughter procedures, indirectly increasing the stress levels at slaughtering, whereas fighting has a direct effect on plasma cortisol, adrenaline and metabolite levels, and meat pH. Other factors such as mixing new and unfamiliar adult cattle during transport or at the lairage and mounting young bulls with each other can also cause muscular fatigue and glycogen depletion [100].

The release of stress hormones causes several physiological changes to degrade meat quality [113]. High concentrations of these hormones cause an acceleration of metabolism of muscle glycogen, therefore, depleting energy levels, which are going to have an impact on the biochemical processes of slaughtered meat [100]. According to Gonzalez-Rivas et al. [114] lower muscle glycogen levels due to stress result in higher ultimate pH values. The low level of glycogen is responsible for the DFD meat, very dark, firm in texture, and dry, with a general low level of glycogen but an extremely high WHC. DFD meat is less attractive to consumers, and it has a shorter shelf life [97]. This can result in tougher meat and is much more prone to having those offensive odors. Generally, according to studies, pre-slaughter stress increases toughness and decreases juiciness, thus making it less palatable for consumers [115].

The industry puts in several strategies to reduce acute and chronic stress in animals at preslaughter to minimize the adverse effects on meat quality. Among them is fasting, whereby the animals are withdrawn from food for a period before slaughter to minimize the instances of gastrointestinal damage and contamination during processing [116]. Proper fasting will ensure that the gut fill remains low while the levels of stress are also kept low, to ensure the maintained meat quality [117].

High ultimate pH values of above 5.8 are typical for DFD meat, since high levels of stress deplete the glycogen stores. Acute stress can also lead to a rapid decrease in post-mortem pH, thus making the PSE condition [112]. This high level of stress may increase the carcass temperature due to increased metabolic activity. The high carcass temperature during the post-mortem period can result in rapid protein denaturation that will, in turn affect the texture and WHC of meat [118]. Adrenaline increases glycolysis rates, thus rapidly producing lactic acid, resulting in a rapid drop in pH immediately after death [119]. Higher levels of adrenalin can lead to rapid initial pH drops, thereby changing the tenderness and color of meat [120]. In chronically stressed animals with high adrenaline levels, the ultimate pH values are usually higher, hence often causing DFD meat [121]. Adrenaline more quickly exhausts the ATP reserves, thereby quickening the setting-in of rigor mortis, thus resulting in tougher meat when time management is not appropriate [112]. The DFD mainly originates from chronic stress, whereby it was observed that when cortisol is elevated for a longer period, it brings forth gross depleting of muscle glycogen reserves. However, acute stress can also result in DFD if it is too close to slaughter and allows no time for replenishment of the glycogen [122].

6 Conclusions

A stress response occurs when the body responds to environmental conditions that have undesirable and harmful consequences for living organisms. In other words, it is a non-specific response in an animal caused by internal and external stressors. The endocrine system is one of the most significant systems that is affected by stressors, which have a significant effect on the physiology of cattle. Hence stress can have a significant impact on livestock performance; practical solutions to reduce these effects should be considered. Animal stress can be reduced through strategies such as limited heat exposure, nutritional, and disease control, which not only increase animal welfare, but also product quality. Farmer education on the effect of stress hormones can help in this respect, to improve cattle breeding management.