Where is it produced and how is it transported?
- Synthesis in the CNS: Corticoliberin is produced by neurons of the parvocellular nuclei located in the medial region of the hypothalamus.
- Transport: The axons of these neurons project to the median eminence. From there, the neurosecretion is released into the hypophyseal portal system, providing a humoral pathway for signal transmission to the adenohypophysis.
- Additional sources: During pregnancy, corticotropin-releasing hormone begins to be secreted by the placenta. Additionally, as the fetal hypothalamic-pituitary system matures, its hypothalamus secretes this hormone.
Mechanism of action and physiological effects
The "corticoliberin — corticotropin — cortisol" axis ensures the body's vital functions during stress, illness, physical and emotional stress, and mental strain.
- Effect on the pituitary gland: Corticoliberin stimulates adenohypophyseal cells that produce proopiomelanocortin. It yields adrenocorticotropic hormone (ACTH), melanocyte-stimulating hormone, $\beta$-endorphin, and other peptides. ACTH, in turn, via membrane G protein-coupled receptors and the adenylate cyclase system, stimulates the zona fasciculata of the adrenal cortex to synthesize and secrete glucocorticoids.
- Role in the nervous system: Within the structures of the central nervous system, the hormone functions as a neurotransmitter and neuromodulator. It is involved in the central regulation of autonomic functions, specifically in the activation of the sympathetic division of the autonomic nervous system.
- Involvement in the initiation of labor: In the fetus, the secretion of hypothalamic corticoliberin stimulates the anterior pituitary, which activates the fetal adrenal glands. The fetal adrenal glands release cortisol and dehydroepiandrosterone sulfate. Cortisol activates phospholipase A2 and cyclooxygenase, leading to the synthesis of prostaglandins PGE2 and PGF2α, while dehydroepiandrosterone sulfate serves as a precursor for the synthesis of estriol in the placenta. Placental estriol prepares the myometrium, and prostaglandins and oxytocin participate in triggering uterine contractions.
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How is corticoliberin secretion regulated?
Regulation occurs via a negative feedback mechanism.
- Stimulating factors: Neurosecretory cells of the hypothalamus are activated under the influence of CNS structures, primarily the limbic system. The system is stimulated by decreased blood glucose levels, trauma, infection, and stress.
- Inhibiting factors: Elevated levels of cortisol inhibit the secretion of corticoliberin in the hypothalamus and ACTH in the pituitary gland.
Clinical significance and pathologies
- Centrogenic adrenal insufficiency: Associated with hypothalamic-pituitary dysfunction. Possible causes include lesions of the hypothalamus and/or pituitary gland: tumors, ischemia, hemorrhage, inherited or congenital developmental anomalies. The pathogenetic basis is a deficiency of corticoliberin and/or ACTH.
- Steroid withdrawal syndrome: Prolonged administration of exogenous glucocorticoids suppresses the body's own hypothalamus-pituitary-adrenal axis, causing profound suppression of corticoliberin and ACTH synthesis. This leads to atrophy of the adrenal cortex. Upon abrupt withdrawal of the drug, the adrenal glands cannot rapidly resume cortisol synthesis, leading to acute adrenal insufficiency: hypotension, hypoglycemia, and shock.
Class and exam questions
What happens to corticoliberin secretion with prolonged glucocorticoid therapy?
Corticoliberin synthesis is profoundly suppressed via a negative feedback mechanism. This leads to a decrease in ACTH levels and subsequent atrophy of the adrenal cortex.
What role does corticoliberin play in the nervous system?
In the CNS, it acts as a neurotransmitter and neuromodulator. It participates in the central regulation of autonomic functions, including the activation of the sympathetic nervous system.
Is corticoliberin produced anywhere other than the maternal hypothalamus?
Yes. During pregnancy, corticotropin-releasing hormone is secreted by the placenta. As the fetal hypothalamic-pituitary system matures, its hypothalamus also secretes corticotropin-releasing hormone.
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What else to study on this topic
- Adrenocorticotropic hormone (ACTH)
- Glucocorticoids and cortisol
- Hypothalamo-pituitary system
- Adrenal insufficiency
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Other topics in "Physiology concepts"
Hormones: definition, classification, and mechanisms of actionEndocrine glands and sources of hormonesChemical structure and synthesis of hormonesSecretion and circulation of hormonesForms of hormonal signal transmissionHormone receptorsHypothalamo-pituitary systemHormones of the neurohypophysisHormones of the adenohypophysis: Growth hormone and prolactinAdrenocortical hormones and ACTHHormones of the adrenal medullaThyroid hormonesHormonal regulation of calcium metabolismPancreatic hormonesSex hormones and the reproductive systemPhysiology of stress and adaptationEndocrine functions of the kidneys, heart, and other organsHypothalamusPhysiology of organs and systemsReceptors and target cellsThyroid hormones and their physiological role
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