Introduction:
Homeostasis preserves stability by maintaining balance and is the cardinal property of all humans. It operates at the cell, tissue, and level of the entire organism. The key variables of homeostasis include glucose levels in the blood, sodium, calcium, oxygen, and core body temperature. These are maintained within the normal range by the endocrine system (regulates functions through hormones) and autonomic nervous systems (ANS, controls involuntary body functions).
Stress is a state of threatened homeostasis triggered by intrinsic or extrinsic stressors. Inherent body and behavioral responses aim to reestablish the body's equilibrium during stress. The adaptive stress response depends upon the interconnected endocrine, cellular, and molecular components, also called the stress system. The primary elements of the stress system are the ANS and hypothalamic-pituitary-adrenal (HPA; involves the hypothalamus, pituitary, and adrenal glands to modulate stress) axis. These elements interact with other central nervous system (CNS) centers to create a successful response against stressors.
How Do Various Body Systems Maintain Homeostasis Under Stress?
All vital body systems are inherently programmed to maintain homeostasis, which is essential for life and well-being. The adaptive stress response of each individual is determined by genetic, environmental, and developmental factors, and changes in the ability to respond to stressors may lead to disease. Moreover, potent chronic (long-lasting) stressors can have detrimental effects on body functions. These include growth, metabolism, reproduction, immunity, behavior, and personality development.
One must note that prenatal life (before birth), infancy, childhood, and adolescence are critical periods in forming an adaptive stress response. It is because of increased vulnerability to stressors during these times.
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Stress system activation triggers a cluster of behavioral and physical changes consistent in their presentation (stress syndrome). Under normal conditions, these changes are adaptive and improve the chances of survival. Initially, the stress system aptly responds to the specific stressor. However, the specificity of the adaptive response decreases following exposure to other potent stressors.
- Behavioral adaptation includes enhanced arousal, alertness, vigilance, and focused attention. Also, physical adaptation mediates a redirection of energy and body resources. Hence, the ANS increases the heart rate, respiratory rate, and fat and glucose metabolism to promote this redirection of vital substrates. On the other hand, energy-consuming functions (digestion, reproduction, growth, and immunity) are temporarily suppressed. As a result, oxygen and nutrients are shifted to the CNS and stressed body sites, where they are the most required.
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Although the entire CNS is involved in fine-tuning the body's homeostasis, specific brain areas have critical and distinct roles in instrumenting the stress response. The central components of the stress system are located in the hypothalamus and the brainstem (a brain part). Stress is mediated by corticotropin-releasing hormone (CRH), adrenaline, and noradrenaline release.
What Are the Effects of Stress on the Homeostatic Systems of the Body?
The stress system is connected to all the major endocrine pathways, including the reproductive, growth, and thyroid. It ensures that endocrine activity is regulated in a coordinated and precise manner. It further serves the adaptive stress response and maximizes the chances of survival against imposed stressors.
1. Reproductive Axis: Stress can negatively impact reproductive function. The male and female reproductive system is inhibited at all levels by stress. CRH suppresses the release of gonadotropin-releasing hormone (GnRH, a regulator of the reproductive pathway) from cells. In addition, glucocorticoids (a type of steroid hormone) exert inhibitory effects on GnRH nerve cells and reproductive organs. Stress also renders the target organs or tissues resistant to the effects of steroids. Thus, steroid formation is directly inhibited at the ovaries and testes level GnRH secretion inhibition from the hypothalamus. It is noteworthy that certain inflammatory mediators (involved in the healing process of the body) can also suppress reproductive function at various levels.
Hence, it provides a link between inflammatory stress and reproductive dysfunction.
In women, stress is responsible for anxiety, depression, eating disorders (bulimia and anorexia), excessive exercise, and bipolar disorder (BPD). Similarly, in men, these effects result in decreased libido and fertility. In addition, stress can also reduce the semen count. In the third trimester of pregnancy, severe depression, anorexia, and Cushing’s syndrome (cortisol excess) are noted due to increased CRH levels in the circulation.
2. Growth Axis: The growth axis is also inhibited during stress at different levels.
Prolonged stress leads to the suppression of growth hormone (GH) secretion and other growth factors. The direct effects of glucocorticoids play a role in the suppression of growth under stress. It is through increased somatostatin (a hormone that inhibits growth) secretion caused by CRH. Somatostatin also contributes to the stress-related suppression of the growth axis. Redirection of oxygen, nutrients, and vital substrates to the brain and other stressed tissues during the adaptive stress response is the probable explanation for the suppressive effects of stress on growth.
Psychosocial dwarfism describes severe childhood or adolescent growth arrest due to emotional deprivation or psychological harassment. It is further associated with behavioral abnormalities such as depression and disturbed eating behaviors. A characteristic finding in this condition is the decreased GH secretion reversible after the removal of the responsible environment.
Another example is the increased risk of delayed growth and development in premature babies after prolonged hospitalization in the neonatal intensive care unit (NICU).
Also, infantile malnutrition is marked by hypercortisolism (raised cortisol levels), decreased responsiveness to CRH, growth arrest, and thyroid function test (TFT) changes. However, these abnormalities usually restore following nutritional rehabilitation.
3. Thyroid Axis: Stress-related inhibition of the thyroid axis is also documented. Chronic stress is associated with decreased thyroid stimulating hormone (TSH, which stimulates the thyroid gland to produce triiodothyronine) and reduction of active triiodothyronine (T3). Studies suggest that increased circulating steroid levels also mediate the stress-induced suppression of the thyroid axis. The suppression serves as energy conservation during the adaptive stress response.
Existing evidence suggests decreased efficacy of TRH (Thyrotropin-releasing hormone) in stimulating TSH release in patients with hypercortisolism. Research states that even a single dose of glucocorticoids can cause an immediate decrease in TSH production in healthy men. In Cushing’s syndrome, the patient’s cortisol excess decreases TSH secretion by reducing its pulsatile release. Conversely, treated Cushing syndrome patients exhibit elevated TSH release. In the case of inflammatory stress, inhibition of TSH secretion may be mediated by the effects of cytokines (inflammatory mediators) on the hypothalamus.
Conclusion:
Despite the multiple challenges in studying stress and homeostasis, it represents a crucial field of research with high value for the prevention and management of various clinical conditions. Strong links exist between behavioral and emotional states relating to stress and autoimmunity, inflammation, cancer, metabolic, reproductive, and growth disorders. Understanding the specific stress system pathways and networks constitutes a step forward in exploring stress-related disease mechanisms. Moreover, clinical evidence strongly supports the impact of acute and chronic stress on homeostasis, highlighting the need for further research in this field.
