A 28-year-old woman has galactorrhea, amenorrhea, and serum prolactin of 180 ng/mL. Dopamine agonist therapy is initiated. What is the receptor-level mechanism by which dopamine reduces prolactin secretion and causes lactotroph cell shrinkage?
- A D1 receptor (Gs-coupled) → increased cAMP → inhibition of prolactin mRNA by negative feedback
- B D2 receptor (Gi-coupled) → reduced cAMP → reduced PKA activity → reduced prolactin gene transcription and exocytosis; also activates K⁺ channels (hyperpolarization) and inhibits Ca²⁺ channels → reduced secretion and cell involution ✓
- C Dopamine binds TRH receptors competitively, blocking TRH-stimulated prolactin release
- D D2 receptor → Gq → PLC → IP3 → Ca²⁺ depletion from ER → reduced secretion
Explanation
Dopamine is the primary physiological inhibitor of prolactin secretion. Lactotrophs express D2 receptors (Gi/Go-coupled). Dopamine binding activates Gi, reducing adenylyl cyclase and cAMP/PKA signaling (lowering transcription of the prolactin gene and vesicle priming). Additionally, Gi/βγ subunits activate inwardly rectifying K⁺ channels (hyperpolarization suppressing vesicle fusion) and inhibit L-type Ca²⁺ channels (reducing the Ca²⁺ trigger for exocytosis). Chronic D2 agonist treatment (cabergoline, bromocriptine) causes lactotroph cell size reduction (involution) via reduced trophic signaling. This explains why pituitary adenomas in prolactinoma can shrink dramatically with dopamine agonists.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.