Hans Selye, an Austrian-Canadian endocrinologist who published more than 39 books and 1,700 articles on stress, is often referred to as the Father of stress research. He is credited with coining the term 'stress', and identifying the hypothalamus-pituitary-adrenal (HPA) axis system, which is the system that is employed by the human body to cope with stress.

Initially, Selye had described stress as a non-specific neuroendocrine response of the body. However, he later omitted the term 'neuroendocrine', as he found that continued exposure to stressors affected most organ systems. He also conducted certain animal studies to study the stress response. In one of the animal studies conducted by Selye, mice were repeatedly injected with insulin. According to Selye, this triggered a stress reaction, which was represented by elevated levels of corticoids and catecholamines, along with some changes that he referred to as the 'triad of stress' (enlargement of the adrenal gland; atrophy of the thymus, spleen and other lymphoid tissue; and gastric ulceration). He initially thought that he was on the verge of discovering a new hormone, but he was proven wrong. During his second year of medical school, Selye observed that several patients experienced common symptoms such as fatigue, appetite disturbance, sleep problems, mood swings, gastrointestinal problems, and diminished concentration and recall, even though they were affected by different illnesses. Thereafter, he attributed these reactions to the body's reaction to the stress caused by the disease. He referred to this collection of symptoms as the stress syndrome. He formulated the General Adaptation Syndrome on the basis of stress syndrome, referring to stress as the common denominator of all adaptive reactions of the body. According to Selye's theory, the presence of a stressor brings about a psychological and physiological state of disruption, which in turn is followed by a series of physiological responses. Dr. Selye was greatly influenced by Walter B. Cannon, which is quite evident from the inclusion of Cannon's concepts of 'fight-or-flight response' and 'homeostasis' in his model. He named his three-stage model of the body's reaction to stress as 'General adaptation syndrome', as the stressors have a general effect on several parts of the body, and the body adapts to stress with the help of its defense mechanism. The use of the term 'syndrome' is attributed to the dependence of the individual manifestations on each other. The adaptive response to stress is divided into three stages. The general adaptation syndrome stages include: ✦ The alarm reaction ✦ The stage of resistance ✦ The stage of exhaustion When the body identifies the presence of a stressor, the HPA axis gets activated. The HPA axis consists of a system of feedback interactions among the hypothalamus, pituitary gland, and adrenal glands. The activated HPA system reacts by producing the flight-or-fight response. During this stage, the hypothalamus stimulates the adrenal-cortical system by releasing the Corticotropin-releasing Factor (CRF), which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH). This is followed by the release of corticoids, such as cortisol and cortisone, by the adrenal cortex of the adrenal glands. The hypothalamus also activates the sympathetic nervous system, which is followed by the release of adrenaline and noradrenaline by the adrenal medulla. The secretion of these hormones brings about the fight-or-flight response that prepares the body to deal with the perceived threat. This response is characterized by: ✦ An increase in the heart rate ✦ Higher blood pressure ✦ An increase in blood glucose levels ✦ Dilation of the pupils ✦ Increased blood flow to the muscles ✦ Increased muscle tension ✦ Suppression of the immune system by cortisol and cortisone ✦ Increased alertness ✦ Reduced production of hormones by the reproductive glands Cortisol, which is also known as the stress hormone, plays a vital role in the stress response of the body. Cortisol is also a part of the inhibitory feedback loop. Once the underlying cause of stress is removed, it blocks the secretion of corticotropin-releasing hormone, thereby preventing the HPA axis interactions. Thus, normalcy can be restored. While the alarm reaction involves the activation or mobilization of the defense mechanisms of the body, the second stage of resistance or adaptation is the stage wherein the body tries to adapt to the stressful stimulus. The body tries to resist the perception of threat with calmness, thereby trying to adapt or cope with the situation in an effective manner. The aim is to achieve homeostasis or the internal balance by reducing the intensity of endocrine and sympathetic activity, which is still higher than normal, but lower than the alarm reaction. During this phase, the affected person tries to adapt to the stressor. This is achieved with the help of the release of glucocorticoids by the adrenal cortex to sustain energy for dealing with the stressor. The body tries to maintain the heart rate, blood pressure, and cardiac output. However, if this phase continues for an extended period, in the absence of periods of rest or relaxation, the body's adaptive energy reserves could get depleted. This can make the affected individual susceptible to disease. As a result, one might experience symptoms such as: ✦ Fatigue ✦ Irritability ✦ Loss of concentration ✦ Lethargy If the stress does not get resolved, one enters the third stage that is called exhaustion. This is the third stage wherein the body's energy reserves and the immunity become exhausted. According to Selye, the continued exposure to stress leads to adrenal exhaustion. The body's defenses become weak, which in turn has an adverse effect on one's physical and emotional health. Chronic stress is associated with high levels of circulating cortisol in the body, which can have an adverse effect on the immune system, digestive system, circulatory system, etc. It can make one susceptible to fatigue and depression. According to Selye, the affected individual is at an increased risk of developing diseases of adaptation at this time. Adrenal exhaustion has an adverse effect on the blood glucose levels. Low blood glucose levels and reduced energy levels are bound to give rise to the following symptoms: ✦ Reduced tolerance to stress ✦ Extreme mental and physical exhaustion ✦ Susceptibility to diseases of adaptation (ulcers, high blood pressure, and heart attacks)