A 32-year-old woman presents with galactorrhoea, amenorrhoea and serum prolactin of 180 ng/mL. MRI shows a 6 mm pituitary lesion. Which physiological mechanism best explains why a dopamine agonist will lower prolactin?

• A Dopamine stimulates somatostatin release, which inhibits prolactin secretion
• B Dopamine increases PIH (prolactin-inhibiting hormone) synthesis in the posterior pituitary
• C Dopamine blocks TRH receptors on lactotrophs, preventing TRH-stimulated prolactin release
• D Dopamine acts on D2 receptors on lactotrophs to inhibit adenylyl cyclase and reduce prolactin gene transcription ✓

Explanation

Dopamine is itself the primary prolactin-inhibiting factor (PIF); it is released tonically from tuberoinfundibular dopaminergic (TIDA) neurons into the portal blood. At lactotrophs, dopamine binds D2 receptors coupled to Gi proteins, inhibiting adenylyl cyclase, reducing cAMP, and suppressing prolactin gene transcription and secretion. Dopamine agonists (cabergoline, bromocriptine) mimic this action. Somatostatin does have minor inhibitory effects but is not the mechanism of dopamine agonist action.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.