Effect of adrenaline on basal and ovine corticotrophin-releasing factor-stimulated ACTH secretion in man

Abstract

Six normal male subjects were given, in single blind random order on six separate occasions, i.v. bolus doses of synthetic ovine corticotrophin-releasing factor-41 (oCRF-41; 25 and 50 micrograms) with and without adrenaline (3 micrograms/min) i.v. for 150 min, the adrenaline infusions alone and saline placebo. The adrenaline infusions resulted in plasma adrenaline concentrations of 4.33 +/- 0.82 (S.E.M.) nmol/l and were associated with an increase in blood glucose, heart rate and systolic blood pressure and a reduction of diastolic blood pressure. Despite these evident biological effects at several sites, there was no stimulation of plasma ACTH or cortisol by adrenaline in comparison with the effect of saline, and no enhancement of the stimulatory effect of either dose of oCRF-41 on ACTH or cortisol secretion. The ACTH response to 50 micrograms oCRF-41 was greater than that to 25 micrograms, indicating that the 25 micrograms dose of oCRF-41 was submaximal and capable of further enhancement. As the plasma adrenaline concentrations during the adrenaline infusions reached the upper limit of the physiological range of plasma adrenaline in man, yet failed to enhance the ACTH or cortisol responses to a submaximal dose of oCRF-41, we conclude that circulating adrenaline neither exerts a direct stimulatory effect on pituitary corticotrophs nor enhances the effect of CRF under physiological circumstances. The adrenaline infusions attenuated the ACTH and cortisol responses to oCRF-41 and were associated with a transient reduction of basal concentrations of both hormones.

The Role of Alpha-2-Adrenoceptors in the Control of ACTH Secretion; Interaction with the Opioid System

“…This requires further investigation. Opiates also inhibit the ACTH response to CRF-41 in man and it has been suggested that this may be due to inhibition of the secretion of endogenous vasopressin, which acts synergistically with CRF-41 [24,35], Naloxone is unlikely to act directly on the corticotrophs, as the stimulant action of this drug is abolished by an alpha-1-antagonist [23]; activation of pituitary adreno ceptors does not stimulate ACTH secretion in man [2,5].…”

“…Plasma cortisol concentrations were measured by radioimmunoassay [5] and plasma adrenaline and noradrenaline concentrations were mea sured by high performance liquid chromatography followed by electro chemical detection [9]. The intra-and interassay coefficients of variation for these assays were all less than 10%.…”

Adrenergic Stimulation of the Human Pituitary-Adrenal Axis Is Attenuated by an Analog of Met-Enkephalin

“…Methoxamine, a highly lipid-soluble rxiadrenoceptor agonist, increases both circulating adrenocortico trophic hormone (ACTH) and cortisol, and this effect is blocked by the specific «i-adrenoceptor antagonist, thymoxamine [1, 2], Furthermore, thymoxamine alone is able to atte nuate diurnal changes in serum cortisol [2], particularly those induced by food [3]. As these effects are not paralleled by the use of epinephrine [4] or norepinephrine [ 1 ], which do not cross the blood-brain barrier, it has been suggested that central (nor)adrenergic pathways stimulate hypothalamic corticotro phin-releasing factor or factors (CRFs) [5].There is also a substantial body of evidence in favour of in hibitory modulation of the hypothalamo-pituitary-adrenal axis by opiates, such as morphine, nalorphine, buprénorphine and codeine [6][7][8][9], and opioid peptides including |J-endorphin and the met-enkephalin analog. £)-Ala2-MePhe'-met-enkephalin-[0]-o 1 (DAMME, FK-33,824) [10][11][12][13], This inhibition can be overcome by high doses of the opiate antagonist, naloxone [7,11,12]; naloxone itself will also elevate plasma ACTH and cor tisol under basal conditions, suggesting the existence of tonic opioid inhibition of ACTH secretion [14][15][16].…”

Modulation of the actions of tyrosine by α2‐adrenoceptor blockade

“…Further studies demonstrated that the a2-and f-adrenoceptor agonist properties of noradrenaline did not account for the differences from methoxamine (Al-Damluji et al, 1987a). Intravenous infusions of adrenaline had no enhancing effect on the activity of synthetic ovine corticotrophin releasing factor in man (Al-Damluji et al, 1987b), in contrast to the findings in cultured rat adenohypophysial cells in vitro (Vale et al, 1983;Giguere & Labrie, 1983). The physiological significance of the stimulant ax-adrenoceptor mechanism on ACTH secretion was demonstrated in 2 situations: the cortisol secretory pattern during waking hours and the ACTH and cortisol secretory responses to food ingestion were both enhanced by intravenous infusions of the al-adrenoceptor agonist -The Macmillan Press Ltd 1988 methoxamine and reduced by the a ,-adrenoceptor antagonist thymoxamine, suggesting that ACTH secretion in these two physiological circumstances is mediated by a1-adrenoceptors (Al-Damluji et al, 1987c,d).…”

“…In six consecutive assays, the lower limit of detection was 4.1 + 0.8 ng IP and the coefficient of variation was 6.0% at 50ngl-P. Plasma cortisol concentrations were measured by radioimmunoassay (Al-Damluji et al, 1987b). The lower limit of detection of this assay is 50nmoll-and the intraassay and interassay coefficients of variation are 4.5% and 8%, respectively.…”