2 Neuroscience2.8 Modulators, hormones and inflammatory responses
2.8.1 The neuroendocrine system
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Written by Resident Doctor Committee · Published
Hypothalamus and pituitary
Parvocellular hypothalamic neurons secrete releasing factors into portal blood, which carries them undiluted to the anterior pituitary.
Magnocellular neurons in the supraoptic and paraventricular nuclei make oxytocin and vasopressin, then release them from axon terminals in the posterior pituitary (neurohypophysis) into systemic blood.
Oxytocin and vasopressin are the only posterior pituitary hormones. Every other pituitary hormone comes from the anterior or intermediate lobe.
The six principal anterior hormones are adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone, luteinising hormone, follicle-stimulating hormone, growth hormone and prolactin.
Peripheral appetite hormones are made in the gut or fat, not the pituitary; leptin, for example, comes from adipocytes.
Hormone | Released by | Action |
|---|---|---|
Vasopressin | Osmolality above about 280 to 285 mOsm/kg; large volume loss | Collecting duct aquaporin-2 (V2); vasoconstriction (V1a) |
Oxytocin | Cervical stretch, suckling | Uterine contraction; milk ejection |
Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal (HPA) axis is a three-level chain, and limbic structures modulate it.
Level | Hormone | Source |
|---|---|---|
Hypothalamus | Corticotrophin-releasing hormone (CRH), augmented by vasopressin | Paraventricular nucleus |
Anterior pituitary | ACTH | Corticotrophs |
Adrenal cortex | Cortisol | Zona fasciculata |
Pro-opiomelanocortin (POMC) is a prohormone cleaved into several active peptides, including ACTH and beta-endorphin.
The amygdala drives CRH release in response to threat, and the hippocampus restrains it.
Cortisol feeds back to suppress both ACTH and CRH.
Plasma cortisol has a circadian rhythm: it peaks in the early morning around waking, about 7 to 7.30 am, and reaches its trough near midnight.
In a healthy person, dexamethasone engages intact negative feedback, suppressing ACTH and so endogenous cortisol. The assay does not measure dexamethasone as cortisol.
After 1 mg dexamethasone overnight, morning cortisol normally falls below about 50 nmol/L.
Non-suppression needs further evaluation: it does not diagnose Cushing's syndrome and also occurs in some depression.
Growth hormone
Somatostatin (growth hormone-inhibiting hormone) from the hypothalamus suppresses growth hormone secretion from anterior pituitary somatotrophs, while growth hormone-releasing hormone and ghrelin drive it.
Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is made mainly in the liver under growth hormone stimulation and feeds back to restrain growth hormone.
Gastrointestinal hormones
Hormone | Source | Actions |
|---|---|---|
Gastrin | Antral G cells | Stimulates parietal cells, largely through histamine from enterochromaffin-like cells |
Somatostatin | Gastric D cells, as antral acidity rises | Holds back gastrin by paracrine action, so inhibits acid |
Cholecystokinin | Upper small bowel, in response to fat and protein | Contracts the gallbladder, relaxes the sphincter of Oddi, stimulates enzyme-rich pancreatic juice and slows gastric emptying |
Glucose-dependent insulinotropic peptide (GIP) | K cells | Acts as an incretin on beta cells |
Gastrin and somatostatin form a negative feedback loop: low antral pH switches gastrin off through somatostatin.
GIP was formerly called gastric inhibitory polypeptide, but it suppresses acid mainly at supraphysiological doses.