Thyrotropin-releasing hormone (TRH)
Also known as: TRH, thyroliberin
A tripeptide from parvocellular paraventricular neurons that stimulates thyrotrophs to release TSH (and lactotrophs to release prolactin) — the top of the hypothalamic–pituitary–thyroid axis.
Overview
TRH (pyroglutamyl-histidyl-prolinamide) is the smallest hypothalamic peptide hormone. It is released from nerve terminals in the median eminence into the primary portal plexus and reaches the anterior pituitary, where it binds the TRH receptor, a Gq-coupled GPCR: phospholipase C generates IP₃ and DAG, raising intracellular Ca²⁺ and activating PKC, which triggers TSH release and synthesis and also promotes correct glycosylation (bioactivity) of TSH.
TRH secretion is set by negative feedback from thyroid hormone: hypothalamic tanycytes convert T4 to T3 with type 2 deiodinase, and T3 suppresses TRH gene expression. Cold exposure (especially in infants) increases TRH, while fasting, illness and glucocorticoids reduce it — part of the reason TSH and T3 fall in starvation and critical illness.
- Location
Source: parvocellular neurons of the paraventricular nucleus → median eminence → portal blood. Targets: thyrotrophs (and lactotrophs) of the anterior pituitary.
Function
- Stimulates synthesis and release of TSH.
- Stimulates prolactin release.
- Acts as a neuromodulator elsewhere in the CNS.
- Physiology
Class: tripeptide. Receptor: TRH-R (Gq → IP₃/Ca²⁺, DAG/PKC). Half-life in plasma only a few minutes; most acts locally in portal blood.
- Regulation
Inhibited by T3/T4 (negative feedback), glucocorticoids and fasting; stimulated by cold, leptin (in the fed state) and the circadian system (TSH peaks at night).
Clinical significance
TRH and hyperprolactinaemia in hypothyroidism
In primary hypothyroidism, raised TRH stimulates lactotrophs, causing hyperprolactinaemia (galactorrhoea, menstrual disturbance) and pituitary enlargement (thyrotroph hyperplasia) that reverse with levothyroxine.
Tertiary hypothyroidism
Hypothalamic disease reducing TRH gives low T4 with low or inappropriately normal TSH (which may have reduced bioactivity).
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.