Activity of melatonin and other pineal indoles on the in vitro synthesis of cortisol, cortisone, and adrenal androgens.
The in vitro effects of 13 indole compounds on the synthesis of glucocorticoids and of adrenal androgens in sheep adrenal glands has been studied from 11-deoxycortisol as a precursor. This work demonstrates the activating effect of some indole compounds on 11 beta-hydroxylase and 17,20-desmolase and the inhibitory effect of most of them on 11 beta-hydroxysteroid dehydrogenase. Three categories could be distinguished: 1) compounds without any effect (5-hydroxytryptophan, 5-hydroxytryptamine); 2) compounds moderately increasing (10-30% as compared with controls) cortisol yields (tryptamine, melatonin, 6-hydroxymelatonin, 5-methoxytryptophol, indomethacin); and 3) compounds markedly increasing (80-100%) cortisol yields (5-methoxyindole acetic acid, 5-hydroxyindole acetic acid, 2-methylindole, 5-hydroxytryptophol, N-acetyl-5-hydroxytryptamine). In fact, since most of the studied indoles reduced 11 beta-hydroxysteroid dehydrogenase activity, the actual activation of cortisol synthesis was four to five times less. Lastly, all the studied compounds, but melatonin, increased the activity of 17,20 desmolase as seen from 11 beta-hydroxyandrostenedione and 11-ketoandrostenedione yields. The possible in vivo effects of the indoles for therapeutic use needs further studying.
Touitou
Y
Y
Department of Biochemistry, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Bogdan
A
A
Auzéby
A
A
Touitou
C
C
D000311:Adrenal Glands / Q000378:metabolism; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D003348:Cortisone / Q000096:biosynthesis*; D005938:Glucocorticoids / Q000096:biosynthesis; D006854:Hydrocortisone / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology*; D010870:Pineal Gland / Q000033:anatomy & histology; D012756:Sheep
D000728:Androgens; D005938:Glucocorticoids; D007211:Indoles; D008550:Melatonin; D003348:Cortisone; D006854:Hydrocortisone