Cortisol · Grey Matter

Cortisol is the steroid hormone of the slow stress response: released by the adrenal cortex at the command of the brain, it mobilises energy, damps inflammation and changes how neurons work for hours, and it rises every morning in a daily rhythm.

Cortisol. Cortisol is the steroid hormone of the slow stress response: released by the adrenal cortex at the command of the brain, it mobilises energy, damps inflammation and changes how neurons work for hours, and it rises every morning in a daily rhythm.

It is the end of the hypothalamic-pituitary-adrenal (HPA) axis. The hypothalamus releases corticotropin-releasing hormone, the anterior pituitary answers with ACTH, and ACTH makes the adrenal cortex synthesise and release cortisol. The whole chain takes minutes, so cortisol peaks well after adrenaline. Being a steroid, it crosses cell membranes and the blood-brain barrier and binds receptors inside cells, mineralocorticoid receptors (high affinity, occupied even at low levels) and glucocorticoid receptors (occupied when levels are high), which act mainly as transcription factors that switch genes on or off.

It closes its own loop. Cortisol acting on the hypothalamus, the pituitary and the hippocampus, which are rich in its receptors, turns the axis down, ending the response.

It follows the clock. Levels are highest around waking (the cortisol awakening response) and lowest in the late evening.

Its effects depend on dose and duration. Moderate, brief rises help memory for significant events; prolonged high levels, in animal studies, shrink dendrites and reduce plasticity in the hippocampus and prefrontal cortex while enlarging dendrites in the amygdala.

Cortisol turns a moment of stress into a state that lasts hours.

Acting on genes, it changes how neurons will behave long after the event that released it.

Questions: How do the fast and the slow stress responses differ? The fast response is nervous: within seconds the sympathetic system drives the adrenal medulla to release adrenaline, and with noradrenaline from sympathetic nerves it raises heart rate, blood glucose and alertness, fading within minutes. The slow response is hormonal: the hypothalamus releases CRH, the pituitary releases ACTH, and the adrenal cortex makes cortisol, which peaks some tens of minutes after the event. Cortisol is a steroid that enters cells and changes gene expression, so its effects last hours, and it ends the response by feeding back on the hypothalamus and pituitary. The first prepares for action now, the second reorganises metabolism, immunity and the brain for what follows. What does prolonged high cortisol do to neurons? Brief rises in cortisol help the brain store important events, but long exposure works differently. In animal studies, weeks of high glucocorticoid levels or chronic stress shorten and simplify the dendrites of hippocampal and prefrontal pyramidal cells and reduce their spines, while dendrites in the amygdala grow. These changes impair learning that depends on the hippocampus and flexible control by the prefrontal cortex, and in animals they largely reverse after the stress ends. Because the hippocampus also helps switch the stress axis off, damage to it can weaken that brake and prolong the exposure.