Which of the following best describes the mechanism by which cortisol exerts negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis?

Explanation

## Cortisol Negative Feedback Mechanism **Key Point:** Cortisol exerts negative feedback at TWO levels of the HPA axis: 1. **Hypothalamic level** — inhibits corticotropin-releasing hormone (CRH) secretion 2. **Anterior pituitary level** — inhibits ACTH secretion ### Mechanism of Action Cortisol binds to **glucocorticoid receptors (GR)** in both the hypothalamus and anterior pituitary cells, suppressing the synthesis and release of CRH and ACTH respectively. This is a classic **negative feedback loop** that prevents excessive cortisol production. ### HPA Axis Hierarchy ``` Hypothalamus (CRH) → Anterior Pituitary (ACTH) → Adrenal Cortex (Cortisol) ↑ | |___________________________________________________| Negative Feedback ``` **High-Yield:** The feedback is **dose-dependent**: - Low cortisol levels → minimal feedback suppression - High cortisol levels → potent suppression of both CRH and ACTH **Clinical Pearl:** Dexamethasone (a synthetic glucocorticoid) is used in the dexamethasone suppression test (DST) to assess HPA axis function by mimicking cortisol's negative feedback effect. **Mnemonic:** **HPA Feedback = H-P-A Suppression** (Hypothalamus and Pituitary are both suppressed by cortisol at the Adrenal level).