Hypothalamic and Pituitary Axes and Layered Feedback
Several anterior-pituitary axes link a hypothalamic hormone, a pituitary tropic hormone and a target gland. In the adrenal axis, cortisol inhibits the two earlier signals. This feedback helps explain responses to gland failure and sustained glucocorticoid treatment.
What a learner can do afterwards
- Traces CRH, ACTH and cortisol through the adrenal axis and identifies cortisol's feedback targets.
- Predicts relative hormone secretion in stated models of adrenal-cortex or anterior-pituitary failure.
- Explains how sustained glucocorticoid treatment can reduce CRH, ACTH and native cortisol production.
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Several axes link the hypothalamus, anterior pituitary and a target gland. A hypothalamic releasing hormone stimulates a pituitary tropic hormone, which stimulates the gland. Tropic means acting on another endocrine gland. Inside responding cells, a receptor signal can activate many relay molecules. This is signal amplification; it does not mean blood hormone concentrations must increase at each gland level.
In the adrenal cortisol axis, the hypothalamus releases corticotropin-releasing hormone, or CRH. CRH stimulates the anterior pituitary to release adrenocorticotropic hormone, or ACTH. ACTH stimulates cortisol secretion from the adrenal cortex. CRH and ACTH are peptides with surface receptors. Cortisol is a steroid with intracellular receptors.
Cortisol inhibits CRH and ACTH release. More cortisol strengthens this negative feedback; less cortisol weakens it. Feedback limits further stimulation, while intracellular amplification increases a cell's response. Suppose the adrenal cortex cannot make enough cortisol, but the upper levels and feedback still work. Cortisol stays low, and reduced inhibition lets CRH and ACTH rise.
Now suppose the anterior pituitary cannot release enough ACTH, while the hypothalamus and adrenal cortex otherwise work. ACTH and cortisol fall. Low cortisol reduces feedback, so CRH can rise, but the pituitary cannot pass on the signal. Unlike adrenal failure alone, this model gives low ACTH. Such patterns help explain results but do not establish a diagnosis on their own.
Sustained glucocorticoid treatment can provide enough feedback to lower CRH and ACTH. Less ACTH stimulation then reduces the adrenal cortex's own cortisol production. Drug activity and native cortisol output are different quantities. Suppression need not be complete; its extent depends on the drug, dose and duration.
CRH stimulates ACTH, which stimulates cortisol. Cortisol inhibits both earlier signals. Predict changes by identifying the interrupted link and the feedback that remains.
This lesson, question bank and flashcards were written for this dataset.
The readings and flashcards were written for this dataset. Linked videos are from Khan Academy and TED-Ed; the thyroid lesson is by Emma Bryce.
More to read
Tracing stimulation through three organs
Follow the hormone released at each stage of the adrenal cortisol axis. CRH comes from the hypothalamus and stimulates the anterior pituitary. The anterior pituitary releases ACTH into blood. ACTH stimulates cortisol secretion from the adrenal cortex.
ACTH is a tropic hormone because it acts on another endocrine gland. The three-organ route describes this axis, not every function of the pituitary.
Cortisol also affects the earlier stages. Its feedback reduces CRH and ACTH release. To understand the system, trace both the stimulation toward the adrenal cortex and the inhibition of the earlier signals.
Comparing two interrupted links
Consider two models with different failed levels. First, suppose the adrenal cortex cannot make enough cortisol, while the hypothalamus, anterior pituitary and feedback responses still work. Low cortisol reduces inhibition. CRH and ACTH rise, but the adrenal cortex cannot provide the expected output.
Next, suppose the anterior pituitary cannot release enough ACTH. With less ACTH stimulation, cortisol falls. An otherwise working hypothalamus can increase CRH in response to reduced feedback, but the failing pituitary cannot pass on that signal.
Both models predict low cortisol. ACTH distinguishes the two stated cases: it rises in adrenal failure and remains low in pituitary failure. These are reasoning models, not diagnoses based on one result.
A receptor signal and a feedback signal
A cell responds to a hormone through a matching receptor. CRH and ACTH are peptides that use surface receptors. Cortisol is a steroid that can act through intracellular receptors and change gene expression.
Within a responding cell, an initial receptor signal can activate many relay molecules. This amplification increases the response. It does not require hormone molecules to grow or successive glands to produce higher blood concentrations.
Negative feedback describes a different relation. Cortisol acts at the hypothalamus and anterior pituitary to reduce the signals that stimulate cortisol production. Amplification and feedback can operate in the same system while having different effects.
Separating drug activity from native output
A glucocorticoid drug can activate feedback responses normally influenced by cortisol. Sufficient activity during sustained treatment can lower CRH and ACTH release. The adrenal cortex then receives less ACTH stimulation and produces less of its own cortisol.
Drug activity and native cortisol production must be considered separately. Strong glucocorticoid effects from treatment can coexist with reduced internal cortisol output.
Suppression varies with the drug, dose and duration. It need not be complete. This feedback explanation does not specify a treatment schedule or predict an individual patient's response.
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