Intracranial dehydroepiandrosterone blocks the activation of tryptophan hydroxylase in response to acute sound stress.
Bilateral infusion of dehydroepiandrosterone (DHEA) given intracerebroventricularly blocked the sound stress-induced increase in tryptophan hydroxylase activity observed ex vivo in midbrain and cortex but had no effect on the level of tryptophan hydroxylase activity from sham-stressed rats. DHEA (20 micrograms total dose) given bilaterally into the region of the central nucleus of the amygdala, 30 min prior to 1 h sound stress, also blocked the increase in enzyme activity in a dose-dependent manner. The DHEA treatment did not alter the activation of the enzyme seen in vitro in the presence of phosphorylating conditions. The effect of DHEA was steroid specific in that other sex steroids, such as estrogen, androgens, or progesterone, were without any effect. Coadministration, 20 micrograms each, of the potent glucocorticoid agonist, RU 28362, with DHEA 30 min prior to 1 h sound stress completely blocked the DHEA suppressive effect on sound stress-induced increases in tryptophan hydroxylase activity. The results obtained suggest that DHEA blocks this increase in tryptophan hydroxylase activity by antagonizing the effects of glucocorticoid.
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0551.
V B
VB
Singh
M
M
Kalimi
T H
TH
Phan
M C
MC
Boadle-Biber
D000161:Acoustic Stimulation; D000208:Acute Disease; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D003687:Dehydroepiandrosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007267:Injections; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors*
D000732:Androstanols; D003687:Dehydroepiandrosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D014365:Tryptophan Hydroxylase