Pituitary stress signal
Adrenocorticotropic hormone (ACTH)
Also searched as Adrenocorticotropic hormone (ACTH).
The missing step: crf does not make cortisol. It makes acth, and acth makes cortisol. Every brain-to-adrenal claim passes through this relay, and it is where the pituitary can amplify or damp the signal independently of what the hypothalamus sent.
In depth
Adrenocorticotropic hormone — the pituitary messenger that carries the stress signal from brain to adrenal gland.
What drives it
Stress-relapse axis increases it.
The actual chain: CRF synthesized in the paraventricular nucleus is transported axonally to the median eminence and released into the hypophyseal portal circulation, where it binds CRHR1 on anterior pituitary CORTICOTROPHS, stimulates POMC transcription, and releases ACTH. CRF does not touch the adrenal. CRHR1 is required: the presence of CRH1 receptors in the pituitary is stated as essential to maintain ACTH secretion. And there is a whole brake: CRH-binding protein (CRH-BP) binds CRH with an affinity greater than the CRH receptors themselves, competitively inhibiting it — a regulator sitting between the peptide and its receptor. But its knockout disappoints, and that is recorded here too: after acute restraint stress, corticosterone and ACTH profiles did not differ in CRH-BP knockout or pituitary-overexpressing mice versus controls — because the system compensated, with PVN CRH and AVP mRNA rising 82 percent and 35 percent in the overexpressing animals. Induced, buffered, not required. And CRF is not alone at the CORTICOTROPH: arginine vasopressin directly stimulates ACTH and synergises with CRF, and vasopressin raises CRHR1 mRNA — so AVP both pushes the same lever and widens it. doi 10.1080/10253890.2017.1322575 · PMC7885796
What it drives
It increases Lowers cortisol.
NBK500031 — ACTH released from the anterior pituitary acts on the adrenal cortex to promote glucocorticoid synthesis and release — primarily cortisol in humans. Glucocorticoids then exert negative feedback on both hypothalamus and pituitary, inhibiting further crh and acth. The feedback wears out, which is the clinically important part: this feedback is transcriptional, via glucocorticoid receptors, and chronic glucocorticoid exposure decreases receptor expression, resulting in reduced negative feedback. Sustained stress degrades its own off-switch.
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.