Touitou Y, Bogdan A, Auzéby A, Touitou C
Department of Biochemistry, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
J Pineal Res. 1989;6(4):341-50. doi: 10.1111/j.1600-079x.1989.tb00430.x.
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.
以11 - 脱氧皮质醇作为前体，研究了13种吲哚化合物对绵羊肾上腺中糖皮质激素和肾上腺雄激素合成的体外作用。这项研究表明，某些吲哚化合物对11β - 羟化酶和17,20 - 裂解酶具有激活作用，而大多数吲哚化合物对11β - 羟类固醇脱氢酶具有抑制作用。可分为三类：1）无任何作用的化合物（5 - 羟色氨酸、5 - 羟色胺）；2）使皮质醇产量适度增加（与对照组相比增加10 - 30%）的化合物（色胺、褪黑素、6 - 羟基褪黑素、5 - 甲氧基色醇、吲哚美辛）；3）使皮质醇产量显著增加（80 - 100%）的化合物（5 - 甲氧基吲哚乙酸、5 - 羟基吲哚乙酸、2 - 甲基吲哚、5 - 羟基色醇、N - 乙酰 - 5 - 羟色胺）。实际上，由于大多数研究的吲哚降低了11β - 羟类固醇脱氢酶的活性，皮质醇合成的实际激活程度降低了四到五倍。最后，从11β - 羟基雄烯二酮和11 - 酮基雄烯二酮的产量来看，除褪黑素外，所有研究的化合物均增加了17,20 - 裂解酶的活性。吲哚在治疗方面的可能体内作用需要进一步研究。
