CRH (Corticotropin-Releasing Hormone)

Where is CRH produced and how does it act?

• Synthesis: Corticorelin is produced by parvocellular secretory neurons located in the periventricular regions of the hypothalamus (hypophysiotropic area). These cells exhibit dual properties: as neurons, they generate electrical impulses, and as endocrine cells, they produce specific neurohormones. Chemically, CRH is a decapeptide. During puberty, these structures mature: close synaptic connections are formed between cells that secrete neurotransmitters and neurons that produce corticorelin.
• Transport: CRH reaches the pituitary gland not via axons, but through a humoral pathway. It is released into the primary capillary plexus, passes through the pituitary portal system, and reaches the secondary capillary plexus of the adenohypophysis. The portal system allows for bidirectional information transfer between the hypothalamus and the pituitary gland.
• Effect: In the anterior pituitary (adenohypophysis), CRH stimulates the synthesis and release of a tropic hormone — ACTH (adrenocorticotropic hormone, or corticotropin).

Regulation of secretion

The functioning of the hypothalamic-pituitary-adrenal axis is based on a cascade principle involving feedback mechanisms.

• Stimulation (+): CRH production is enhanced by decreased blood glucose levels, trauma, and infection.
• Inhibition (-): Mediated by negative feedback. Elevated levels of cortisol inhibit the secretion of corticorelin in the hypothalamus and ACTH in the pituitary. Hypothalamic dopamine exerts an inhibitory effect on CRH secretion. A decrease in this dopaminergic inhibition leads to increased ACTH production.

Clinical significance and pathologies

• CRH hyperproduction: Excess corticorelin resulting from traumatic brain injury or neuroinfections affecting the hypothalamus leads to hypersecretion of ACTH and bilateral adrenal cortex hyperplasia. This results in central hypercortisolism, known as Cushing's disease. Hypercortisolism causes systemic disturbances in protein, fat, carbohydrate, and electrolyte metabolism: increased gluconeogenesis, steroid diabetes, hypokalemic acidosis, and disproportionate obesity with a moon face and fat deposition on the neck and upper trunk. In children, varying degrees of virilization may occur, while in adults, signs of virilization appear later. In the digestive system, excess glucocorticoids cause a neurohumoral shift: hypersecretion of gastric juice, suppression of mucus production, and inhibition of gastric mucosal regeneration.
• CRH deficiency: Observed in secondary (centrogenic, hypothalamo-pituitary) endocrine disorders. Hypothalamic lesions, including tumors, ischemia, hemorrhage, and congenital developmental anomalies, lead to a deficiency of corticorelin.
• Therapeutic application: Suppressive glucocorticoid therapy operates on the negative feedback principle: it inhibits the secretion of CRH and ACTH, thereby suppressing the endogenous production of hormones by the adrenal cortex (steroidogenesis).

Class and exam questions

What else to study on this topic

• Adenohypophysis and its hormones
• ACTH (Adrenocorticotropic Hormone)
• Glucocorticoids (Cortisol)
• Cushing's disease
• Pituitary portal system

Other topics in "Physiology concepts"

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