L6 - Adrenal Cortex

Introduction to the Adrenal Cortex

• Focus on the adrenal cortex, a key area in endocrine pharmacology.

• Review of physiology covered in previous studies (Chapter 33).

• Learning Outcomes:

  • Understand the hypothalamic-pituitary-adrenal (HPA) axis.

  • Describe adrenal gland endocrine functions.

  • Link mechanisms to clinical and adverse effects of glucocorticoids and other hormones.

  • Mechanism of action for antagonists and adrenal cortex synthesis inhibitors.

Overview of Adrenal Glands

• Small but critical structures situated atop each kidney.

• Composed of two regions:

  • Adrenal Cortex: Produces steroid hormones (glucocorticoids, mineralocorticoids, adrenal androgens).

  • Adrenal Medulla: Part of the sympathetic nervous system, releases catecholamines (epinephrine, norepinephrine).

• Role of adrenal cortex:

  • Glucocorticoids (e.g., cortisol): Regulate long-term stress response, metabolism, and immune function.

  • Mineralocorticoids (e.g., aldosterone): Control blood pressure and fluid balance by regulating sodium and potassium levels.

  • Adrenal Androgens: Influence secondary sexual characteristics and reproductive functions.

Hypothalamic-Pituitary-Adrenal (HPA) Axis

• The cortex plays a role in managing stress responses through hormone regulation.

• Function of the HPA axis:

  • Stress detected by the hypothalamus triggers CRF release.

  • CRF stimulates ACTH release from the anterior pituitary gland.

  • ACTH induces cortisol secretion from the adrenal cortex.

  • Cortisol modulates stress responses and is kept in check to prevent excessive release.

Physiological Effects of Cortisol

• Crucial for homeostasis and stress adaptation.

• Metabolic Functions:

  • Promotes gluconeogenesis (glucose production) in liver and kidneys.

  • Enhances lipolysis, providing energy through fat breakdown.

  • Increases protein catabolism for glucose substrate, potentially leading to muscle wasting if prolonged.

• Anti-inflammatory Effects:

  • Suppresses pro-inflammatory cytokines and immune response.

  • Chronic elevated cortisol may weaken immune defenses.

• Cardiovascular Effects:

  • Maintains blood pressure by enhancing blood vessel sensitivity to catecholamines.

  • Excessive cortisol can lead to hypertension.

• Impact on Mood and Behavior:

  • Influences memory (especially in the hippocampus) and emotional regulation.

  • Short-term increases in cortisol can enhance focus; chronic elevation may lead to anxiety and cognitive impairment.

Mechanism of Action of Corticosteroids

• Corticosteroids regulate gene transcription by binding to intracellular receptors.

• The glucocorticoid receptor (GR alpha) is activated upon binding.

• This complex translocates to the nucleus, binds to glucocorticoid response elements (GREs), and induces/represses gene transcription, affecting various physiological processes.

Mineralocorticoids Function

• Regulate electrolyte balance, blood pressure, and fluid volume.

• Primary regulation via the renin-angiotensin system and potassium levels.

• Mechanism of action:

  • Increases sodium reabsorption and potassium excretion in the kidneys, contributing to blood volume regulation.

Disorders Related to Adrenal Function

Addison's Disease

• Caused by a deficiency in corticosteroids (e.g., cortisol) due to autoimmune damage.

• Symptoms: extreme fatigue, low blood pressure, dehydration, and hyperpigmentation.

• Treatment: hormone replacement therapy (hydrocortisone).

Cushing's Syndrome

• Caused by excessive glucocorticoids, leading to high cortisol levels.

• Symptoms: rapid weight gain, moon-shaped face, hypertension, thinning skin.

• Treatment: glucocorticoid synthesis inhibitors or surgical removal of tumors.

Conn's Syndrome

• Caused by excess aldosterone production (often from a benign tumor).

• Symptoms: sodium retention, potassium loss, increased blood pressure, excessive thirst, and urination.

• Treatment usually involves antagonists or surgery.

Pharmacological Agents Related to Adrenal Cortex

• Corticosteroids: utilized for their anti-inflammatory and immunosuppressive properties, crucial in various conditions like transplant rejections and autoimmune disorders.

• ACTH: Used diagnostically to assess adrenal cortical function; synthetic analogs are preferred due to stability.

• Adrenal Cortex Synthesis Inhibitors: These are used for testing or treating conditions like Cushing's syndrome.

• Aldosterone Antagonists: Utilized in conditions like Conn's syndrome, often have potassium-sparing properties.

Adverse Effects of Long-term Corticosteroid Use

• Increased Infection Risk: Immunosuppression leading to higher susceptibility.

• Cushing's Syndrome: Mimics effects of excess cortisol due to prolonged use.

• Osteoporosis: Can lead to bone loss and increased fracture risk.

• Growth Suppression: In children, long-term use can inhibit bone growth.

• CNS Effects: Short-term use may induce euphoria; long-term may cause mood disturbances and cognitive impairment.

Summary of Key Concepts

• Cortisol and its regulation within the HPA axis are essential for various physiological functions, especially under stress.

• Awareness of diseases related to adrenal dysfunction is crucial for effective diagnosis and treatment planning.

• Pharmacological agents affecting the adrenal cortex play significant roles in managing endocrine disorders but require careful monitoring for adverse effects.