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Every morning, your cortisol rises before you even wake — and your brain has to tell that ordinary rhythm apart from a genuine emergency, using nothing but the same one hormone. It manages this with two separate receptors that respond to cortisol at very different concentrations. The mineralocorticoid receptor is already almost full at the low, everyday levels cortisol sits at for most of the day — it is reading the routine rhythm. The glucocorticoid receptor barely engages until cortisol surges, whether from the normal morning peak or from real acute stress — it is the one that actually signals a stress response.

Cortisol acts on two distinct receptor types. The mineralocorticoid receptor (MR) has a high affinityHow strongly a drug binds to its receptor.Read more → for cortisol (it binds cortisol readily, even at low concentration), so it is substantially occupied even at normal, low basal cortisol levels throughout the day — a tonic (constant, always-on) signal. The glucocorticoid receptor (GR) has a much lower affinity, so it only becomes strongly occupied once cortisol rises during acute stress — a phasic (occurring in a burst, tied to a specific event) signal. In the morning cortisol peak or during a stressful event, GR occupancy rises sharply while MR occupancy was already near its ceiling. GR-mediated negative feedback on the hypothalamusA small brain structure that controls basic functions like hunger, temperature, sleep and hormone release.Read more → and pituitary is also what the dexamethasone suppression test (giving a synthetic steroid, dexamethasone, and checking whether it correctly switches off the body's own cortisol production) is built to probe.

• A description of a cortisol receptor occupied even at low, basal hormone levels points to the mineralocorticoid receptor.
• A description of a receptor that only becomes substantially occupied once cortisol rises during acute stress points to the glucocorticoid receptor.
• A case linking chronic cortisol excess to hippocampal changes in depression is describing glucocorticoid receptor-mediated overactivation.
• A question about dexamethasone suppression testing and which receptor mediates the feedback is asking about the glucocorticoid receptor.

• Mineralocorticoid receptor (MR) vs glucocorticoid receptor (GR) — MR has high affinityHow strongly a drug binds to its receptor.Read more → and is near-saturated at normal basal cortisol; GR has low affinity and only fills once cortisol rises during stress.
• Glucocorticoid receptor (GR) vs corticotropin-releasing hormone receptor — GR responds to circulating cortisol at the target tissue; the corticotropin-releasing hormone receptor sits further upstream, in the pituitary, responding to corticotropin-releasing hormone rather than cortisol itself.
• Mineralocorticoid receptor (MR) vs its 'usual' hormone, aldosterone — cortisol circulates at far higher concentration than aldosterone, so in most tissues cortisol, not aldosterone, is the dominant ligand actually occupying MR — except in the classic mineralocorticoid tissues (kidney, colon), where 11-beta-hydroxysteroid dehydrogenase type 2 inactivates cortisol locally so that aldosterone reaches MR; that enzyme is why liquorice raises blood pressure.

Assuming there is only one type of cortisol receptor — cortisol genuinely signals through two, with very different affinities. Confusing which receptor is high-affinityHow strongly a drug binds to its receptor.Read more →: MR is the high-affinity, basal-tone receptor, not GR. Assuming the mineralocorticoid receptor only responds to aldosterone — in the brain and at normal cortisol levels, cortisol itself is the dominant ligand for MR because cortisol circulates at much higher concentration than aldosterone.

When a stem gives you a receptor's affinityHow strongly a drug binds to its receptor.Read more → or its occupancy pattern relative to hormone level, map it onto the basal-versus-stress framework rather than memorising isolated facts — high affinity plus basal occupancy always points to the mineralocorticoid receptor, and low affinity plus stress-triggered occupancy always points to the glucocorticoid receptor.