The Effects of Endogenous Catecholamines on the Hypothalamo-Pituitary Adrenal Axis in Man

Abstract

Our previous investigations of the effects of catecholamines on the secretion of ACTH in man demonstrated that intravenous infusion of the α₁-adrenoceptor agonist methoxamine stimulated the secretion of ACTH in a dose-dependent manner and the effect was blocked by a concomitant administration of the α₁-adrenoceptor antagonist thymoxamine. The site of action of these stimulant (α₁-adrenoceptors appears to be in the central nervous system; the effects of methoxamine are not reproduced by equipotent doses of the more hydrophylic a α₁-adrenoceptor agonist noradrenaline, which reaches the pituitary gland and the median eminence following a systemic injection, but does not cross the blood-brain barrier (1). Further studies demonstrated that the α₂- and β-adrenoceptor agonist properties of noradrenaline did not account for the differences from methoxamine (1). Intravenous infusions of adrenaline had no enhancing effect on the activity of synthetic ovine corticotrophin releasing factor in man (2), which is in contrast to the findings in cultured rat adenohypophysial cells in vitro (3,4). The physiological significance of the stimulant α₁-adrenoceptor mechanism on ACTH secretion was demonstrated in two situations: the Cortisol secretory pattern during waking hours and the ACTH and Cortisol responses to food ingestion were both enhanced by intravenous infusions of the α₁-adrenoceptor agonist methoxamine and reduced by the a α₁-adrenoceptor antagonist thymoxamine, suggesting that under these two physiological circumstances, ACTH secretion is mediated by α₁-adrenoceptors (5,6). In our current studies, we have been examining the effects of endogenous catecholamines on the hypothalamo-pituitary adrenal axis in man.