Chapter 04Regulation

Cortisol's partners

Cortisol does not act alone. Some molecules turn down its production, some soften its effects once released, and some sit on the other end of the see-saw.

Begin
Fig. 04 · The stress axis
negative feedback Hypothalamus Pituitary Adrenal cortex Body tissues CRH ACTH Cortisol DHEA / DHEA-S Testosterone
sleep suffers CORTISOL MELATONIN
−Turns it downBuffers its effectNegative feedback
Optimal04 · Regulation

The stress axis

Cortisol is made at the end of a chain. The hypothalamus releases CRH, the pituitary releases ACTH, and the adrenal cortex releases cortisol, which then acts on tissues throughout the body.

Its partners work at different points along this chain.

Upstream

Cortisol is its own brake

Cortisol has its own negative feedback loop. Once the job is done, it switches off the signals upstream that called for it.

Upstream · act on CRH, ACTH or the adrenal

Turning production down

Oxytocin
↓ ACTH and ↓ cortisol, at rest and under stress; dose dependent. Also calms the stress response in the brain.
ANP
Atrial natriuretic peptide: ↓ CRH, ↓ ACTH, ↓ cortisol.
Beta-endorphin
↓ ACTH, ↓ cortisol.
Upstream

Quieting the drive

GABA
Quiets the hypothalamic drive.
Endocannabinoids
Dampen HPA activation.
Melatonin
Opposes cortisol across the day–night cycle.
Downstream

Buffering the effect

Cortisol is still released, but its downstream actions are buffered.

DHEA / DHEA-STestosterone
The see-saw

Melatonin vs. cortisol

When one is high the other should be low. Evening cortisol that stays up keeps melatonin down, and sleep suffers.

Switch between morning, evening and a stressed evening above the diagram.

Potentially therapeutic

Several of cortisol's partners are potential treatments. Hover one to see where it acts.

Oxytocin DHEA ANP Melatonin Testosterone Beta-endorphin CBD THC · mixed effect