Neuroendocrine regulation of the hypothalamic-pituitary-adrenocortical axis: Where does atriopeptin fit in?

Atriopeptin has a complete preclinical portfolio in rodents as a hypothalamic regulator of adenohypophyseal ACTH secretion. At least four laboratories have reported that atriopeptin suppresses ACTH and cortisol levels in humans. In behavioural studies of rodents and humans, atriopeptin appears to be an anxiolytic, as well as panicolytic. Despite the weight of this evidence, the role of atriopeptin as an inhibitory regulator of the HPA axis and as an antistress substance overall is largely ignored. This paper critically reviews the evidence outlined above and attempts to identify the reasons for the muted enthusiasm for atriopeptin in the field. Overall, the lack of well-defined physiologic or pathophysiologic paradigms, as well as the scarcity of pharmacological tools, appear to be the main culprits.