Thyrotropin-Releasing Hormone (TRH)

TRH, or Thyrotropin-Releasing Hormone, is a tripeptide hormone (meaning it’s made of three amino acids) produced by the hypothalamus — the brain’s master regulator of hormone activity.

Its main role is to stimulate the anterior pituitary gland to release TSH (Thyroid-Stimulating Hormone), which in turn stimulates the thyroid gland to produce thyroid hormones: T3 (triiodothyronine) and T4 (thyroxine).

🧠 How TRH Works: The HPT Axis (Hypothalamus–Pituitary–Thyroid Axis)

1. The hypothalamus releases TRH into the hypophyseal portal system.
2. TRH travels to the anterior pituitary gland.
3. TRH binds to receptors on pituitary cells, prompting the release of TSH.
4. TSH stimulates the thyroid gland to produce and release T3 and T4.
5. T3 and T4 regulate metabolism, energy use, body temperature, and development.

🔁 Feedback Loop:

✅ Negative Feedback Control:

• When T3 and T4 levels are high, they inhibit further TRH and TSH release.
• When T3 and T4 are low, the hypothalamus releases more TRH to increase thyroid activity.

This loop helps maintain stable thyroid hormone levels in the body.

🧪 Clinical Relevance of TRH

✅ TRH Is Used For:

• TRH stimulation test: formerly used to assess pituitary or thyroid function (now largely replaced by simpler TSH and free T4 tests).
• Understanding causes of hypothyroidism (whether due to thyroid, pituitary, or hypothalamic issues)

🧠 TRH Also Affects:

• Prolactin release: TRH can mildly stimulate prolactin secretion, especially under certain conditions.
• Mood and sleep regulation (as a neurotransmitter in the brain, though these effects are less understood)

📉 Low TRH May Indicate:

• Hypothalamic dysfunction or damage
• Tertiary hypothyroidism (rare – when the thyroid underfunction is caused by the hypothalamus not making TRH)

📈 High TRH May Indicate:

• Low thyroid hormone levels (as a compensatory signal)
• Resistance to thyroid hormone or pituitary disorders causing overproduction of TSH

🧠 Summary Table: