UPSC MainsZOOLOGY-PAPER-II201315 Marks
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Q23.

Mention the hypothalamic-adenohypophysial secretions that stimulate, sustain and regulate adrenal cortex functions. Add a note on feedback systems.

How to Approach

This question requires a detailed understanding of the hypothalamic-pituitary-adrenal (HPA) axis. The answer should begin by outlining the key hormones involved – CRH, ACTH, and cortisol – and their respective roles. It should then explain how these hormones stimulate, sustain, and regulate adrenal cortex function. Crucially, the answer must address the feedback mechanisms (both negative and, to a lesser extent, positive) that maintain hormonal homeostasis. A structured approach, detailing each hormone’s action and the feedback loops, is recommended.

Model Answer

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Introduction

The adrenal cortex, responsible for producing vital glucocorticoids, mineralocorticoids, and androgens, is critically regulated by the hypothalamic-pituitary-adrenal (HPA) axis. This intricate neuroendocrine system ensures appropriate responses to stress and maintains overall physiological balance. Disruptions in this axis can lead to a range of disorders, including Cushing’s syndrome and Addison’s disease. Understanding the secretions that govern adrenal cortex function, and the feedback mechanisms that control them, is fundamental to comprehending endocrine physiology and pathology. This answer will detail the hypothalamic and adenohypophysial secretions involved in stimulating, sustaining, and regulating adrenal cortex functions, alongside a discussion of the feedback systems that govern this axis.

Hypothalamic Control: Corticotropin-Releasing Hormone (CRH)

The hypothalamus initiates the HPA axis cascade by secreting Corticotropin-Releasing Hormone (CRH). CRH is a peptide hormone that acts on the anterior pituitary gland, specifically corticotroph cells. Its primary function is to stimulate the synthesis and secretion of Adrenocorticotropic Hormone (ACTH). Factors influencing CRH release include stress (physical and psychological), circadian rhythms, and signals from other brain regions like the amygdala and hippocampus.

Adenohypophysial Control: Adrenocorticotropic Hormone (ACTH)

Adrenocorticotropic Hormone (ACTH), secreted by the anterior pituitary gland in response to CRH, is the primary regulator of the adrenal cortex. ACTH travels through the bloodstream to the adrenal glands and binds to melanocortin 2 receptors (MC2R) on adrenal cortex cells. This binding initiates a cascade of events leading to:

  • Stimulation of cortisol synthesis: ACTH increases the expression of enzymes involved in cortisol production, particularly cholesterol side-chain cleavage enzyme (P450scc), which is rate-limiting in cortisol synthesis.
  • Sustained adrenal cortex function: Chronic ACTH stimulation leads to hypertrophy and hyperplasia of the adrenal cortex, increasing its capacity for cortisol production.
  • Regulation of adrenal blood flow: ACTH increases blood flow to the adrenal cortex, enhancing the delivery of precursors needed for cortisol synthesis.

Adrenal Cortex Hormones and their Functions

The adrenal cortex produces three main classes of steroid hormones:

  • Glucocorticoids (primarily cortisol): Involved in glucose metabolism, immune suppression, and stress response.
  • Mineralocorticoids (primarily aldosterone): Regulate electrolyte balance (sodium and potassium) and blood pressure.
  • Androgens (primarily DHEA): Contribute to the development of secondary sexual characteristics and have some anabolic effects.

ACTH primarily stimulates the production of glucocorticoids, but also influences the secretion of mineralocorticoids and androgens to a lesser extent.

Feedback Systems Regulating the HPA Axis

Negative Feedback

The HPA axis is tightly regulated by negative feedback loops, primarily involving cortisol. High levels of cortisol exert inhibitory effects at two key levels:

  • Pituitary Level: Cortisol directly inhibits the release of ACTH from the anterior pituitary, reducing the responsiveness of corticotrophs to CRH.
  • Hypothalamic Level: Cortisol inhibits the release of CRH from the hypothalamus, further suppressing ACTH secretion.

This negative feedback ensures that cortisol levels do not become excessively high. The sensitivity of the pituitary and hypothalamus to cortisol varies throughout the day, contributing to the circadian rhythm of cortisol secretion.

Positive Feedback (Limited Role)

While primarily regulated by negative feedback, some evidence suggests a limited role for positive feedback in specific situations. For example, during severe stress, cortisol can enhance the sensitivity of the hypothalamus to CRH, potentially amplifying the HPA axis response. However, this positive feedback is transient and does not override the dominant negative feedback mechanisms.

Other Regulatory Factors

Beyond CRH and ACTH, other factors influence the HPA axis:

  • Vasopressin (AVP): Released from the posterior pituitary, AVP can synergize with CRH to stimulate ACTH release, particularly during stress.
  • GABA and Serotonin: These neurotransmitters can modulate HPA axis activity, with GABA generally inhibitory and serotonin having complex effects.
Hormone Source Target Effect
CRH Hypothalamus Anterior Pituitary Stimulates ACTH release
ACTH Anterior Pituitary Adrenal Cortex Stimulates cortisol, aldosterone, and androgen synthesis
Cortisol Adrenal Cortex Hypothalamus & Anterior Pituitary Negative feedback inhibition of CRH & ACTH release

Conclusion

The hypothalamic-adenohypophysial regulation of the adrenal cortex is a complex and vital system for maintaining homeostasis. CRH and ACTH act as key intermediaries, stimulating and sustaining adrenal function, while cortisol provides crucial negative feedback to prevent overproduction. Understanding these interactions, and the influence of other regulatory factors, is essential for comprehending the physiological response to stress and the pathophysiology of adrenal disorders. Further research continues to refine our understanding of the nuances within this critical neuroendocrine axis.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

HPA Axis
The Hypothalamic-Pituitary-Adrenal (HPA) axis is a neuroendocrine system that controls reactions to stress and regulates many body processes, including digestion, the immune system, mood, and energy expenditure.
Corticotrophs
Corticotrophs are specialized cells within the anterior pituitary gland responsible for the synthesis and secretion of adrenocorticotropic hormone (ACTH) in response to corticotropin-releasing hormone (CRH).

Key Statistics

Approximately 1-5% of the population experiences Cushing’s syndrome, a condition characterized by prolonged exposure to high levels of cortisol.

Source: National Institute of Neurological Disorders and Stroke (NINDS), 2023 (Knowledge Cutoff)

Approximately 80-90% of cortisol in the bloodstream is bound to corticosteroid-binding globulin (CBG), a protein produced by the liver.

Source: Guyton and Hall Textbook of Medical Physiology, 13th Edition (Knowledge Cutoff)

Examples

Addison’s Disease

Addison’s disease, characterized by adrenal insufficiency, demonstrates the importance of the HPA axis. Damage to the adrenal glands leads to insufficient cortisol production, disrupting the negative feedback loop and resulting in increased CRH and ACTH levels. Symptoms include fatigue, weakness, and hypotension.

Frequently Asked Questions

What happens if the negative feedback loop fails?

If the negative feedback loop fails, cortisol levels can become chronically elevated, leading to Cushing’s syndrome. This can result in a variety of health problems, including weight gain, muscle weakness, and increased risk of infection.

Topics Covered

BiologyEndocrinologyHormonesAdrenal GlandFeedback Systems