What is the Origin of Glucocorticoid Receptor Feedback?

The concept of endocrine feedback loops is central to physiology, dating back to early 20th-century experiments that demonstrated the reciprocal relationship between hormone levels and gland activity. The specific role of the glucocorticoid receptor in mediating this negative control was elucidated through molecular and pharmacological studies of the stress response system. It provides a cellular explanation for systemic endocrine control.

What is the Mechanism of Glucocorticoid Receptor Feedback?

Cortisol, a lipophilic steroid, easily crosses cell membranes and binds to the intracellular GR, forming a complex that translocates to the nucleus. Once in the nucleus, this complex acts as a transcription factor, binding to glucocorticoid response elements (GREs) to suppress the gene expression of CRH and ACTH. The efficacy of this feedback mechanism determines the speed and robustness of the HPA axis recovery following an acute stressor.

Glucocorticoid Receptor Feedback ∞ Area

Glucocorticoid Receptor Feedback

Meaning

Glucocorticoid receptor feedback is the fundamental homeostatic mechanism by which circulating glucocorticoids, primarily cortisol, regulate their own production and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Elevated cortisol levels bind to glucocorticoid receptors (GRs) in the hypothalamus and pituitary, inhibiting the release of CRH and ACTH, respectively. This negative feedback loop is crucial for terminating the stress response and preventing prolonged hypercortisolemia, which is catabolic and immunosuppressive. Dysfunction in this feedback is a hallmark of chronic stress and certain endocrine pathologies.