Keywords

1 Introduction

Environment is a complex system, comprising multiple elements networking among each other. Out of the wide network of components, climate happens to be of paramount importance. Climate is constituted of photoperiod, temperature, humidity, solar radiation, etc., which strongly governs the behavioral patterns of animals. The climatic factors induce neuroendocrinal responses in animals, thereby affecting their health and production.

Environmental stress consists of physical ‘abiotic’ characters, such as climatic factors, toxins, and radiation or ‘biotic’ character, such as parasites and competitors (Kristensen 2004). The physiology of stress involves three systems directly; the nervous, the endocrine, and the immune, all of which can be prompted by perceived threats (Everly 2002). Stress is viewed as a general biologic and usually functional response to environmental and bodily demands. Adaptations to demands of physical environment through behavioral; physiologic; neuroendocrine; and metabolic responses, so as to maintain homeostasis, are a general biologic phenomenon in animals. Cannon (1915) was the pioneer in bringing the concept of adaptation linking the brain, behavior, and endocrine system to light. Seyle (1946) emphasized on the role of adrenal cortex as the chief coordinator of nonspecific bodily response to stress. This concept led to the idea that the level of corticosteroids in blood reflects the state of stress in an organism. General adaptation syndrome (Seyle 1950), hypothesizes an alarm, a resistance, and an exhaustion phase of stress response of adrenal gland.

In the tropical and sub tropical environment, heat stress is the most vital climatic stress that adversely affects livestock. Heat stress with high humidity, tends to further disturb animal physiology. Animals employ some response mechanisms to adapt to the hot climate and although these mechanisms are helpful for survival, they are detrimental to animal productivity. Exposure to different environmental stressors elicits various physiologic changes. These changes are either recognized as emergency, activating adrenomedullary system and releasing catecholamines or general adaptation response in which pituitary-adrenal axis is activated to release corticosteroids.

The adrenal gland has been known to be influenced by the environment, more than any other endocrine glands of the body. Changes in the external environmental stimuli (photoperiod, sound, temperature, etc.) and emotional or traumatic stress appear to increase the activity of the hypothalamo-hypophyseal-adrenal axis (HHAA), resulting in increased adrenocortical/medullary activity. In the area of endocrine research, thrust investigations are presently being carried out to establish relationship between Pineal-Adrenal and Pineal-Adrenal-Immune system.

Pineal gland is recognized as a neuroendocrine organ transducing circadian rhythm/cyclic photic input, which affects seasonal changes in reproductive capability of various species (Reiter 1991). Substantial data have been gathered to illustrate the participation of pineal gland in a variety of extra-reproductive processes (Johnson 1982) wherein, pineal-adrenal, pineal-thyroid, and pineal-immune (PI) system interplay are the most attractive areas of scientific exploration. Pineal-adrenal liaison research dates back to the discovery of adrenoglomerulotropin in pineal extracts of rats (Farrell 1960). Ever since then, researchers have made attempts to set up the possible role of the pineal gland in influencing the (HHAA), (Mess 1983). Early on, proposition of a bilateral relationship between the pineal and adrenal glands or melatonin and corticosteroids was reinforced by experimental and clinical findings suggesting that melatonin may ably protect organisms against stress-induced pathologies (Khan et al. 1990).

It has been suggested that melatonin may act as an important regulator of adrenal functions (Touitou et al. 1989; Vaughan 1984). Glucocorticoids are one amid other endogenous compounds that have been shown to influence melatonin production in various vertebrates (Bauer et al. 1989; Demisch et al. 1988; Zawilska and Sadowska 2002). In vivo and in vitro experiments revealed a suppressive action of melatonin on glucocorticoids production and release (Ogle and Kitay 1978; Vaughan et al. 1972). They also aid termination of stress response by acting at extrahypothalamic regulatory centers, the hypothalamus and the pituitary. The negative feedback mechanism of glucocorticoid on adrenocorticotrophic hormone (ACTH) secretion tends to limit the duration of total tissue exposure to glucocorticoid, thereby playing down its catabolic, lipogenic, antireproductive and immunosuppressive effect (Tsigos and Chrousos 2002).

Extensive research has been conducted to establish the PI system interactions. It has been indicated by in vivo and in vitro experiments that pineal gland, via its hormone melatonin, boosts immune responses (Guerrero and Reiter 2002; Nelson 2004). In fact, the PI axis involving melatonin and immunocompetent cells, is an integral part of innate immune response (Markus et al. 2007). Melatonin possesses the ability to upregulate the immunosuppression although not directly on immunocompetent cells, but mediated via the endogenous opioid system upon antigen activation of T cells (Pierpaoli and Maestroni 1987). Furthermore, melatonin is required for photoperiodic regulation of circulating leukocytes and neural immune interactions that mediate several aspects of immune functions (Wen et al. 2007). Melatonin plays significant immunomodulatory role in immunocompromised animals and also stimulates production of cytokines (Guerrero and Reiter 2002). Corticosteroids possess potent immuno-suppressive properties in lymphocytes both in vitro and in vivo (Cupps and Fauci 1982). Melatonin reverses the depression of antibody response induced by corticosterone (Maestroni et al. 1988).

2 Pineal Gland and its Significance

Pineal gland is a small endocrine gland, situated in the caudal portion of the third ventricle. It is white in color and pinecone shaped. It is also called pineal body, epiphysis cerebri, epiphysis or the “third eye” because of its light-transducing ability. The importance of the pineal gland was recognized long ago in the 16th century and the gland was thought to be the seat of the soul. However, it is only in the past three decades that remarkable advances in the knowledge of the functional significance of the epiphysis have been made (Vincenzo et al. 1996). René Descartes, who dedicated much time to the study of the pineal gland, called it the “seat of the soul.” He believed that it was the point of connection between the intellect and the body.

Histologically, the pineal is composed of pinealocytes and glial cells. Pinealocytes produce and secrete serotonin derivative of melatonin, a hormone that plays a major role in sexual development, hibernation in animals, metabolism, and seasonal breeding. The pineal regulates circadian rhythms or biologic rhythms through the secretion of melatonin. Seasonal changes, which bring forth changes in day length have profound effects on reproduction in many species, and melatonin is the key player in controlling such events. The reproductive function shows both qualitative and quantitative differences especially in the seasonal cycle in both females and males. This feature is especially evident in animals that breed seasonally. Observed variations in the reproductive cycle reveal that breeding periods are timed by changes in the photoperiod. The pineal regulates seasonal changes in the reproductive function of these animal species through its endocrine activity (Reiter 1991; Weaver et al. 1993). Long-day breeders, such as the hamster, are reproductively active during the summer (Silman 1993). Because reproductive regression was associated with the extended period of melatonin elevation, the terms antigonadal or antigonadotrophic were commonly applied to melatonin. Antigonadal action is exerted by inhibition of gonadotrophin-releasing hormone (GnRH) (Buchanan and Yellon 1991). In contrast, in short-day breeders, such as the sheep, are engaged in reproductive activity (breeding season), which is associated with autumn and winter seasons with decreased day length. Melatonin exerts a stimulatory effect on the reproductive axis in these species (Karsch et al. 1984) and can be referred to as being progonadotrophic (Coelho et al. 2006; Wagner et al. 2008; Chemineau et al. 2008). In addition, melatonin receptors have been identified in hypothalamic neurons governing the release of pituitary gonadotrophs (Roy et al. 2001; Dubocovich and Markowska 2005 ), in gonadotropins of the anterior pituitary (Johnston et al. 2003; Balik et al. 2004), and in both female and male gonads (Woo et al. 2001; Frungieri et al. 2005).

Melatonin may play a protective, anti-stress role in the gastric mucosa via a mechanism involving the central nervous system and may inhibit the induction of gastric ulcers by restraining stress or centrally administered thyrotropin releasing hormone (TRH). Both in vitro and in vivo experiments show that the pineal gland, via its hormone melatonin, enhances immune function. Mechanism involved in the immunostimulatory effect is not well understood, but some evidences suggest the existence of specific binding sites for melatonin on immune cells. Additionally, in both in vitro and in vivo experiments, melatonin has been found to protect cells, tissues, and organs against oxidative damage induced by a variety of free radical generating agents and processes. Melatonin’s function as a free radical scavenger (Tan et al. 1993) and antioxidants is likely assisted by the ease with which it crosses morphophysiologic barriers, e.g., the blood–brain barrier, and enters cells and subcellular compartments (Hardeland 2005). Melatonin has been reported to stimulate/alter the activities of enzymes (Rodriguez et al. 2004), which improve the total antioxidative defense capacity of the organism, i.e., superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), glucose-6-phosphate dehydrogenase, and nitric oxide synthase (NOS). Melatonin, ubiquitously acting as antioxidant has implications for the optimal function of cells and organs, including those of the reproductive system (Tamura et al. 2008). Although the direct free radical scavenging actions of melatonin are accomplished without an interaction with specific receptors, the stimulatory effects of melatonin on antioxidative enzymes are likely mediated either by membrane receptors or by nuclear- or cytosol-binding sites (CBS) (Tomas-Zapio and Coto-Montes 2005).

Melatonin participates in homeostasis by controlling the level of proliferation and differentiation of cells and thereby preventing the growth of malignant cells (Sanchez Barcelo et al. 2003). Melatonin is highly lipophilic and its effects on tumor cells are independent of melatonin receptor mediated pathway. Experimental studies revealed that melatonin controls the cell proliferation by regulating both the intracellular growth stimulating hormone (GSH) and nitric oxide (NO) levels, both of which are essential for the maintenance of homeostasis (Stephanie et al. 2002). Melatonin prevents cancerous growth by potentiating the immunocompetent mechanism (Vijayalaxmi et al. 2002). Melatonin has also been shown to influence the growth of natural killer (NK) cells through interleukin-2 (IL-2) production and this action explains melatonin’s antiproliferative effect. NK cells play an important role in immunosurveillance against the development of tumors and metastases (Srinivasan 2000; Vijayalaxmi et al. 2002).

3 Pineal Gland Secretions

The pineal gland contains a number of peptides, including GnRH, TRH, oxytocin, and vasotocin, along with a number of important neurotransmitters, such as somatostatin, norepinephrine, serotonin, and histamine. Apart from these hormones, there are other peptides, such as tryptamine, 5-methoxytryptamine, epithalamine and epithalon, that are secreted from the pineal gland (Sibarov et al. 2002), The major pineal hormone, however, is melatonin, a derivative of the amino acid tryptophan. Figure 9.1 represents the schematic description of synthesis of melatonin.

Fig. 9.1
figure 1

Schematic description of synthesis of melatonin. The synthesis of melatonin takes place in the pinealocytes, the cellular units of the pineal gland. Biosynthesis of melatonin starts with the active absorption of amino acid tryptophan from the blood. At first, 5-hydroxy-tryptophan is formed through tryptophanehydroxylase (TH). Subsequently, the transformation into serotonin (5-hydroxy-tryptamine) takes place by the enzyme aromatic-amino-acid-decarboxylase (AAMD). The next step is the transformation of serotonin into N-acetylserotonin through N-acetyl-transferase (NAT) as the limitating step for melatonin synthesis. Finally, the synthesis of melatonin (N-acetyl-5-methoxy-tryiptamine) through the enzmye hydroxyindole-O-methyltransferase (HIOMT) takes place

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4 Pineal-Adrenal Relationship

Stress is expressed as a response of an organism to external stimuli or change. The most often used nomenclature defines environmental stimuli that lead to an imbalance of homeostasis as “stressor” and the corresponding defense reaction of an animal as “stress response” (Mostl and Palme 2002). Different types of stressors may elicit varying degrees of responses in animals. The cellular and molecular mechanisms underlying these specific responses tailored for individual circumstances present a major challenge for the future. During stress, various endocrine responses are involved to soothe the individual. The front-line hormones that overcome stressful situations are the glucocorticoids and catecholamine. The secretion of glucocorticoids is a classic endocrine response to stress (Kannan et al. 2000). Currently, it appears that glucocorticosteroids provide an initial integrating signal, which in conjunction with other hormones and paracrine secretions may determine specific behavioral and physiologic responses that help the animal adapt to different environmental conditions (Wingfield and Kitaysky 2002). There are recent reports, which suggest the involvement of melatonin in heat stress relief or tolerance in farm animals (Collier et al. 2008; Sejian et al. 2008a). Furthermore, there is evidence in support of the role of melatonin and prolactin in the up-regulation of heat shock protein 70 (HSP 70) expression during heat stress (Collier et al. 2008).

During thermal stress, glucocorticoids can modify the level of melatonin in the body so that the anti-stress action of melatonin could be enhanced. The action of glucocorticoids on the level of pineal melatonin shows that a mechanism exists for glucocorticoids to act on the pineal to control level of melatonin (Sejian et al. 2008b). In addition, melatonin may act as an important regulator of adrenal function (Sejian et al. 2010a; Sejian et al. 2010b; Sejian and Srivastava 2010a). In vitro and in vivo experiments revealed a suppressive action of melatonin on adrenal glucocorticoid production and release. The relationship between the rhythm of plasma melatonin and cortisol as well as the presence of the melatonin receptors on adrenal cortex indicates a direct effect of melatonin on steroidogenesis. Pineal extracts have been shown to inhibit adrenal beta hydroxylase activity, thus, blocking the synthesis of aldosterone, cortisol and cortisone, but not deoxycortisone (Lommer 1966). Melatonin has been shown to reduce the production of 4-3-ketonic corticosteroids from endogenous precursors in vitro and to suppress aldosterone production (Gromava et al. 1967). However, some studies have shown that pineal extracts elevate aldosterone production (Sejian and Srivastava 2010a). Administration of the pineal hormone melatonin to growing female rats provided significant protection against the injurious effects of glucocorticoid dexamethasone. The increased glutamic pyruvic transaminase (GPT), free fatty acids, triglyceride, and glucose levels caused by glucocorticoid were reversed by administration of melatonin. It is proposed that the protection offered by melatonin against the injurious effects of dexamethasone is due to a direct anti-glucocorticoid action and does not involve any other endocrine organ (Mori et al. 1984). Zwirska-Korczala et al. (1991) reported that pinealectomy abolishes the rhythmic character of corticosterone secretion and alters the circadian rhythms of T3, T4 and testosterone secretion. Exogenous melatonin was shown to have a suppressive effect on the diurnal secretion of T3, T4, and testosterone in pinealectomised rats but stimulated rhythmic corticosterone secretion.

Troiani et al. (1988) observed that subcutaneous administration of saline into the hind leg of rats at night elicited a decrease in N-acetyl transferase (NAT) activity and melatonin content of the pineal gland. This decrease in pineal melatonin production after saline injection was prevented by adrenalectomy. The adrenal mediated depression in melatonin synthesis may be elicited by adrenal cortical hormone corticosterone and apparently does not involve any chemicals released from adrenal medulla. Sudhakumari et al. (2001 ) showed that pineal, adrenal, and gonadal weights exhibited cyclical patterns relative to pineal gland activity, which also correlated with plasma levels of melatonin, corticosterone, and gonadal steroids in Jungle bush quail. They also observed that increased photoperiod, ambient temperature, and rainfall were positively correlated with adrenal and gonadal functions and inversely related to pineal gland activity. Pineal gland is known to have anti-stressogenic effect in mammals and birds. It is also known to have a tranquilizing effect on animals. Melatonin is included in the feed of pigs raised in commercial piggeries to protect them against occurrence of peptic ulcers. There are also report indicating role of melatonin to upregulate HSP 70 gene expression during heat stress (Collier et al. 2008). Experimental data indicate that melatonin has anti-stress properties in goats. The significant effect of synthetic glucocorticoid on melatonin level during thermal stress establishes the relationship between these two endocrine glands. Given the importance of thermal stress in hampering animal productivity in tropical countries, this finding has potential impact on the revenue of commercial and subsistence farmers.

5 Pineal-Adrenal-Immune System Relationship

In recent years, much attention has been devoted to the possible interaction between pineal gland, adrenal gland, and the immune system (Esquifino et al. 2004; Maestroni 2001; Guerrero and Reiter 2002). Maestroni et al. (1986) first showed that inhibition of melatonin synthesis causes inhibition of cellular and humoral responses in mice. The diurnal and seasonal changes in the immune system have been shown to correlate with melatonin synthesis and secretion (Skwarlo-Sonta 2002). Melatonin is synthesized by human lymphocytes and this finding adds further support to the hypothesis that melatonin plays a role in the regulation of the human immune system (Carrillo-Vico et al. 2004). Melatonin also plays a significant role in guarding the non-specific responses of laboratory animals and birds (Paredes et al. 2007; Sanchez et al. 2004). Melatonin provides a functional link between the neuroendocrine and immuno-hematopoietic systems (Claustrat et al. 2005).

During the last 20 years, the number of published papers unfolding bidirectional interrelationships between the pineal gland, melatonin, and the immune system has increased several folds (Conti and Maestroni 1994), most of them aimed to elucidate the mechanism(s) involved. In humans, there is evidence showing an inverse relationship between plasma melatonin and cortisol circadian rhythms. The connection between rhythms of plasma melatonin and cortisol as well as the occurrence of melatonin receptor on adrenal cortex can be taken as a validation for direct effects of melatonin on steroidogenesis (Torres-Farfan et al. 2003). Mechanisms which melatonin uses to influence immune system function are complex, but include participation of mediators (endogenous opioids, cytokines, hormones, zinc pool) as well as specific binding sites on the immune cells. Melatonin, being a highly lypophilic compound, may also penetrate immune cells without mediation of specific receptors. By synthesizing and secreting soluble factors, cytokines, the immune system may influence pineal gland function and thereby closing the information loop that sustains homeostasis during harmful environmental conditions.

Deciphering the melatonin message within the body is critical to adapt to the physiologic functions of an animal to environmental conditions and needs, and this adaptation would increase the probability of its survival. Previously, immune system was considered to function autonomously, but now ample experimental evidences support bidirectional interactions with the nervous and endocrine systems (Goetzl and Sreedharan 1992; Fabris 1994; Homo-Delarche and Dardenne 1993). Adrenal corticosteroids were the first hormonal factors considered to be regulators of the diurnal rhythm of the immune system. There is substantial evidence, which shows that particular subtypes of immune cells and other immune parameters fluctuate differentially over a 24 h period and exhibit different phase relationships with circulating corticosteroid levels (Angeli et al. 1990; McNulty et al. 1990; Levi et al. 1992). Thus, a three-way coordination between the pineal gland, adrenal gland, and immune system is well explored through scientific tools. Figure 9.2 describes the pictorial representation of pineal-adrenal-immune system relationship.

Fig. 9.2
figure 2

Pictorial representation of pineal-adrenal-immune system relationship. The adrenal cortex hormone cortisol inhibits both melatonin as well as immune functions. However, pineal hormone melatonin stimulates both adrenocortical secretions as well as immune functions. Immune system has positive feedback stimulation on pineal melatonin secretions

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6 Experimental Findings for Pineal-Adrenal-Immune Relationship Under Thermal Stress

One approach to study the functional involvement of pineal-adrenal-immune system in alleviating stress in animals is to investigate changes, which occur in these animals after suppressing the production of major hormonal products from the pineal-adrenal-immune system (Sejian 2007). Schematic representations of three experimental technical details that depict pineal-adrenal-immune system relation hypothesis have been described in Fig. 9.3.

Fig. 9.3
figure 3

Schematic representations of experimental technical details to fulfill pineal-adrenal-immune system relationship. This relationship is established in three different ways (1) Suppressing adrenal cortex secretion by metyrapone and administering melatonin, (2) Suppressing adrenal cortex secretion by metyrapone and administering pineal proteins and (3) Suppressing pineal secretions by propranolol and administering hydrocortisone

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6.1 Chemical Adrenalectomy and Melatonin Administration

Pineal-adrenal relationship can be established by suppressing the production of endocrine secretions from one gland while exogenously administering the other gland hormone in excess to understand if this resumed the normal secretion of already suppressed gland. Chemical adrenalectomy can be achieved by injecting metyrapone followed by exogenous melatonin treatment to support pineal-adrenal association under thermal stress (Sejian and Srivastava 2010b). Metyrapone and melatonin treatments can significantly affect levels of glucose, total protein, total cholesterol, cortisol, and aldosterone in the plasma. Metyrapone treatment can aggravate thermal stress in animals, but administration of melatonin ameliorates the condition (Sejian and Srivastava 2010c). This validates the role of melatonin in relieving thermal stress in goats (Sejian and Srivastava 2010b).

Mean plasma cortisol showed an upward trend on heat exposure (Sejian and Srivastava 2010c 2010a), which declined after metyrapone and melatonin treatments. This was similar to the findings reported by Aggarwal et al. (2005) in cattle. It was observed that melatonin plays an important role in the regulation of adrenal hormones in cattle during summer. Furthermore, the depressive effect of melatonin on adrenal glands as determined by changes in the medullary and cortical hormones in cattle was established. Konakchieva et al. (1997) reported that melatonin attenuates the adrenocortical response to stress and influences the biosynthesis, release, and glucocorticoid responsiveness of hypothalamic ACTH secretagogues. Mean plasma aldosterone in goats decreased markedly after thermal stress due to combined activities of metyrapone and melatonin. Furthermore, these treatments significantly (P < 0.05) increased the phagocytic activity of peripheral neutrophils in goats (Sejian and Srivastava 2010b). This finding on non-specific immune response by melatonin in goats agrees with Hriscu (2005), who reported a physiologic role of melatonin in increasing the phagocytosis percentage of neutrophils and hinted potential existence of several pineal–hypothalamic pathways regulating different components of phagocytosis in vivo. Several reports suggest the role of melatonin in influencing phagocytosis through its receptor mediated action on the phagocytes (Rodriguez et al. 2001; Paredes et al. 2007). There are several reports indicating exogenous melatonin administration enhancing the cell-mediated immune response to a contact antigen (Lopes et al. 2001; Malhotra et al. 2004; Srinivasan et al. 2005; Varga et al. 2008). Markus et al. (2007) further reported that immune–pineal axis is an integral part of innate immune response, which involves the sequential involvement of pineal melatonin and immune-competent cells.

There was remarkable decrease in cortisol level after metyrapone treatment, which was further reduced by melatonin administration, indicating the attenuating effect of melatonin on adrenal corticoids (Sejian and Srivastava 2010c). In response to metyrapone and melatonin treatments, an increase in aldosterone level was observed. These results reiterate the stress relieving properties of melatonin and the role of pineal gland in adrenal cortical functions. Further studies on this will help us understand the functional relationship between pineal, adrenal, and immune system, and how this relationship modulates the non-specific immune response for the well-being of goats during thermal stress. Table 9.1 describes the effect of heat stress, metyrapone and melatonin treatment on endocrine parameters.

Table 9.1 Effect of heat stress, metyrapone and melatonin treatment on endocrine parameters
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6.2 Chemical Adrenalectomy and Pineal Protein Administration

Sejian and Srivastava (2010d) conducted a study to establish the probable anti-stress effect of total precipitated pineal proteins (PP) in goats. Biochemical parameters, enzyme profile, and non-specific immune responses were used to study animals housed in psychrometric chamber with temperature and relative humidity (RH) conditions of 40°C and 60%, respectively for a period of 17 days. Chemical adrenalectomy was achieved by injecting animals with appropriate concentrations of metyrapone followed by exogenous total precipitated PI treatment. Thermal stress and chemical adrenalectomy significantly affected glucose, total protein, total cholesterol, and ALP contents of plasma. In addition, thermal stress, chemical adrenalectomy, and PP affected phagocytosis index (PI) (Garcia-Perganeda et al. 1999). While thermal stress decreased the PI, metyrapone and pineal protein treatments increased the levels of PI. Administration of total precipitated PP and metyrapone to stressed induced animals successfully relieved adverse affects of heat stress on the animals (Sejian and Srivastava 2010d). Table 9.2 describes the effect of heat stress, metyrapone and PP treatment on endocrine parameters.

Table 9.2 Effect of heat stress, metyrapone, and pineal protein treatment on endocrine profile in goats
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6.3 Pinealectomy and Hydrocortisone Administration

Sejian et al. (2008a) also established the pineal-adrenal-thyroid-immune interaction of goats by suppressing the pineal secretions chemically and administering hydrocortisone exogenously under heat stress. Chemical pinealectomy was achieved in goats by injecting propranolol intravenously followed by exogenous hydrocortisone treatment upon exposure to thermal stress. On subjecting the animals to thermal stress, the level of melatonin increased significantly. Perhaps, higher concentration of melatonin is required to combat the stressful condition in order to maintain the homeothermy. This shows the protective role of melatonin during thermal stress. Further, melatonin plays an important role in thermoregulation (John et al. 1978). Barriga et al. (2002) reported direct effect of corticosterone on pinealocytes in reducing melatonin level. From this, it is evident that, glucocorticoids have direct action on pinealocytes to alter melatonin level. Hence, during adverse pinealectomy condition in these goats, glucocorticoids could have stimulated the pinealocytes to release melatonin in these animals in order to relieve thermal stress (Sejian and Srivastava 2010e). Propranolol and hydrocortisone treatments also influenced plasma T3, and T4 concentrations indicating the role of melatonin in controlling thyroid gland hormones (Sakamoto et al. 2000; Abecia et al. 2005). Table 9.3 describes the effect of heat stress, propranolol, and hydrocortisone treatment on endocrine parameters.

Table 9.3 Effect of heat stress, propranolol and hydrocortisone treatment on endocrine parameters
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Chemical pinealectomy significantly affected plasma levels of plasma glucose, total protein, total cholesterol, cortisol, insulin, aldosterone, melatonin, and corticosterone and these could be significantly counteracted by administration of hydrocortisone (Sejian et al. 2008a). Furthermore, propranolol and hydrocortisone treatments also significantly affected levels of plasma calcium, ACP, ALP, and PI (Sejian et al. 2008b; Sejian et al. 2010c). The decline of PI after pinealectomy could be attributed to the reduction in pineal secretions, such as melatonin, which modulates phagocytosis in macrophages (Kanchev et al. 2006; Roy et al. 2001). This finding establishes profound influence of pineal gland on the non-specific immune response. Hydrocortisone counteracted the effect of propranolol treatment by increasing the phagocytosis index, showing immunopotentiative nature of glucocorticoids in the absence of pineal endocrine secretions. The immunostimulative capacity of glucocorticoids with non-specific immune response was reported by Forner et al. (1995). Furthermore, it has been shown by several researchers that pineal gland and its hormone, melatonin, play central role in the control of the circadian organization of hypophysial-adrenal and immune system (Reiter 1995; Karasek 2004). Propranolol treatment aggravated thermal stress; although administration of hydrocortisone could ameliorate the condition. This indicates the role of pineal in support of thermoregulation. These results establish the modulating effects of glucocorticoids on pineal activity to relieve thermal stress in goats.

7 Conclusions

Pineal gland and its secretions, melatonin and PP, play the central role in the control of the circadian organization of hypophysial–adrenal and immune system. Experimental data generated from various studies have helped researchers in the field to understand the functional relationship among pineal, adrenal, and immune system, and how these relationships modulate stress and non-specific immune response for the well-being of animals (goats) under thermal stress. Notably, melatonin and PP play vital roles in mitigating negative impacts of thermal stress in animals. The effect of glucocorticoids on melatonin levels during thermal stress establishes the relationship between these two endocrine glands under heat stress. As thermal stress is the most significant factor influencing livestock production in tropical countries, understanding the endocrine relationship that plays a major role in relieving such stress could pave the way for improved livestock production to improve the economy of farm households and underprivileged farmers.

8 Future Scope of Research

It has become evident that there exists an elaborate interplay between the pineal-adrenal-immune system axis, the details of which need to be experimentally proved. Further detailed studies are required to fully understand the mechanisms of interactions between these glands (pineal-adrenal, pineal-adrenal-immune system etc.). It is still not apparent whether melatonin controls thermal stress by acting directly on adrenal cortex or by acting on hypothalamus or anterior pituitary. In addition, there are some unanswered questions on whether there is a direct link between glucocorticoids and melatonin production and secretion. If one attempts to establish this multi-gland relationship, research and experiments should be conceived in such a way to unveil the precise mechanism of the interactions among pineal, adrenal, and immune system.