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Control of Stress-Induced ACTH Secretion by Vasopressin and CRH: Additional Evidence

Adriana T Ramos1, Sergio Tufik, Lanfranco R P Troncone

  • 1Department of Psychobiology, Universidade Federal de Sx00E3;o Paulo (UNIFESP), Sx00E3;o Paulo, Brazil.

Neuropsychobiology
|May 26, 2016
PubMed

Insights

Combining vasopressin (V1b) and corticotropin-releasing factor (CRF1) receptor antagonists fully blocks ACTH secretion under various stress conditions. This dual blockade offers a potent strategy for managing stress-related hormonal responses.

Area of Science:

  • Neuroendocrinology
  • Stress Physiology

Background:

  • Vasopressin and CRH are key regulators of the hypothalamic-pituitary-adrenal (HPA) axis.
  • These hormones play complementary roles in adrenocorticotropic hormone (ACTH) secretion under diverse stress types.

Purpose of the Study:

  • To investigate the combined efficacy of V1b and CRF1 receptor antagonists in inhibiting ACTH secretion.
  • To determine the differential effectiveness of each antagonist against specific stress modalities.

Main Methods:

  • Rats were subjected to ether vapor inhalation, restraint stress, or forced swimming.
  • Plasma ACTH levels were measured after co-administration of CRF1 antagonist SSR125543 and V1b antagonist SSR149415.
  • The duration of the inhibitory effect was assessed.

Main Results:

  • Combined V1b and CRF1 antagonists completely inhibited ACTH secretion across all tested stress types.
  • SSR125543 was effective against restraint stress, while SSR149415 targeted ether inhalation stress.
  • Both antagonists were required to block the ACTH response to forced swimming stress.
  • SSR125543 demonstrated a prolonged duration of action.

Conclusions:

  • Concomitant blockade of V1b and CRF1 receptors provides a comprehensive inhibition of ACTH secretion.
  • The combination therapy is effective against a range of acute stressors.
  • SSR125543 shows potential for prolonged HPA axis blockade strategies.

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