Physiology · Hypothalamo-Pituitary Axis and Neuroendocrine Integration

A 28-year-old woman presents with amenorrhoea, galactorrhoea, and a serum prolactin of 180 ng/mL. MRI reveals a 6 mm pituitary microadenoma. Which of the following best explains the physiological mechanism by which hypothalamic dopamine normally suppresses prolactin secretion?

  • A Dopamine binds D1 receptors on lactotrophs, activating Gs protein to increase cAMP and stimulate prolactin degradation
  • B Dopamine activates hypothalamic somatostatin neurons that then directly inhibit lactotroph secretion via SRIF receptors
  • C Dopamine binds D2 receptors on lactotrophs, activating Gi protein to reduce cAMP and inhibit prolactin gene transcription
  • D Dopamine blocks TRH release from the hypothalamus, thereby removing the primary prolactin secretagogue
Correct answer: C. Dopamine binds D2 receptors on lactotrophs, activating Gi protein to reduce cAMP and inhibit prolactin gene transcription

Explanation

Dopamine (also called prolactin-inhibiting factor, PIF) released from tuberoinfundibular neurons reaches lactotrophs via the portal circulation and binds D2 receptors coupled to Gi protein; Gi inhibits adenylyl cyclase, lowers intracellular cAMP, reduces PKA activity, and consequently suppresses both prolactin synthesis and release. A microadenoma escapes this tonic inhibition, hence hyperprolactinaemia. D1 receptors couple to Gs (stimulatory), not inhibitory. TRH is a weak prolactin secretagogue but not the primary regulator; and somatostatin does not mediate dopamine's lactotroph effect.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.

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