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Biol Pharm Bull. 2013;36(2):228-37.
Effect of Polyphenols on Production of Steroid Hormones from Human Adrenocortical NCI-H295R Cells.
Hasegawa E, Nakagawa S, Sato M, Tachikawa E, Yamato S.
Source
Department of Bio-Analytical Chemistry, Niigata University of Pharmacy and Applied Life Sciences.
Abstract
Modulating steroid hormone levels is a curative and preventive measure for Cushing's syndrome, aldosteronism, and various stress-triggered symptoms. Polyphenols have been reported to inhibit steroidogenic enzymes such as 3β-hydroxysteroid dehydrogenase (3β-HSD) and aromatase. However, evidence for their inhibitory effects is fragmentary because it has been determined in studies with small groups of steroid hormones. To investigate the effects of steroids on complete steroidogenic pathways, comprehensive analysis of steroid hormones is necessary. Here we cultured forskolin-stimulated NCI-H295R, a human adrenocortical carcinoma cell line, in the presence of a polyphenol and employed GC-MS to simultaneously determine the levels of nine steroid hormones (pregnenolone, progesterone, deoxycorticosterone, aldosterone, 17α-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, and estradiol) in cell culture supernatant. We found that daidzein, genistein, apigenin, hesperetin, naringenin, and eriodictyol significantly reduced deoxycorticosterone and androstenedione levels (p<0.05), suggesting inhibition of 3β-HSD by these polyphenols. Apigenin was more potent than other polyphenols in increasing the levels of pregnenolone and 17α-hydroxyprogesterone, suggesting that it inhibits cytochrome P450 (CYP) 17 and CYP21, as well as 3β-HSD. Real-time reverse transcription polymerase chain reaction showed that apigenin significantly downregulated the expression levels of 3β-HSD, CYP17, and CYP21 mRNA (p<0.05). This is the first study to demonstrate the inhibitory effects of apigenin on CYP17 and CYP21.
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For example, daidzein, genistein, apigenin, and naringenin inhibit 3β-hydroxysteroid dehydrogenase (3β-HSD).9–11) while daidzein and genistein inhibit cytochrome P450 (CYP) 21.12) In addition, isoflavones inhibit both 3β-HSD
and 17β-hydroxysteroid dehydrogenase (17β-HSD).13
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Accordingly, we tested the effects of polyphenols on steroido-
genic pathways by simultaneously measuring levels of nine
steroid hormones. We found that isoflavones (daidzein and ge-
nistein), one flavone (apigenin), and three flavanones (hesper-
etin, naringenin, and eriodictyol) dose-dependently decreased
the levels of androstenedione and deoxycorticosterone pro-
duced by forskolin-stimulated NCI-H295R cells, suggesting inhibition of 3β-HSD. These inhibitory effects were in good 9 –11)
agreement with the results of previous studies.
Comprehensive understanding of steroidogenic pathways is important to understand the actions of pharmaceutical agents
inhibition of 3β-HSD. These inhibitory effects were in good 9 –11)
agreement with the results of previous studies.