Acetaldehyde, a metabolite of ethanol, activates the hypothalamic-pituitary-adrenal axis in the rat.
Cyanamide is a potent inhibitor of aldehyde dehydrogenase (ALDH: EC 1.2.1.3) used in the treatment of alcoholics. In the presence of ethanol, cyanamide causes an accumulation of acetaldehyde, a highly toxic metabolite of ethanol, with unpleasant side-effects. A similar accumulation is seen in some Oriental people with low ALDH activity. We have investigated the effects of ethanol and cyanamide administration on the activation of the hypothalamic-pituitary-adrenal (HPA) axis using in situ hybridization histochemistry and radioimmunoassay. Ethanol plus cyanamide resulted in a significant increase in corticotrophin-releasing factor and arginine vasopressin mRNA in the paraventricular nucleus, and pro-opiomelanocortin mRNA in the anterior pituitary. Plasma corticosterone concentrations were also significantly elevated following ethanol plus cyanamide administration. The blood concentration of acetaldehyde in the ethanol plus cyanamide group increased significantly. These results suggest that acetaldehyde, induced by blocking ethanol metabolism, is able to activate the HPA axis operating through a central mechanism.
Kinoshita
H
H
URC for Neuroendocrinology, University of Bristol, BRI, Marlborough Street, Bristol BS2 8HW, UK.
Jessop
D S
DS
Finn
D P
DP
Coventry
T L
TL
Roberts
D J
DJ
Ameno
K
K
Jiri
I
I
Harbuz
M S
MS
D000079:Acetaldehyde / Q000097:blood*; D000818:Animals; D001127:Arginine Vasopressin / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D003484:Cyanamide / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D000431:Ethanol; D003484:Cyanamide; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone; D000079:Acetaldehyde; D003345:Corticosterone