Flavonoid inhibition of overexpressed human 3β-hydroxysteroid dehydrogenase type II

Ohno, Shuji; Matsumoto, Noriko; Watanabe, Moe; Nakajin, Shizuo

doi:10.1016/j.jsbmb.2003.11.007

Cited by 43 publications

(23 citation statements)

References 38 publications

(35 reference statements)

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“…Apigenin markedly increased pregnenolone and 17α-hydroxyprogesterone levels and slightly increased DHEA levels, while dose-dependently decreasing androstenedione and deoxycorticosterone levels, suggesting inhibition of 3β-HSD, CYP17, and CYP21. There are reports of daidzein, genistein, apigenin, and naringenin inhibiting 3β-HSD, [9][10][11] and similar reports of daidzein and genistein inhibiting CYP21. 12) However, the inhibitory effect of apigenin on CYP17 and CYP21 has not yet been reported.…”

Section: Genistein (G) Apigenin (A) Hesperetin (H) Naringenin (N)mentioning

confidence: 64%

“…7) Several polyphenols have been shown to have inhibitory effects against steroidogenic enzymes; for example, daidzein, genistein, apigenin, and naringenin act against 3β-HSD, while isoflavones act against 3β-HSD and aromatase. [9][10][11][12][13] In these reports, only one or two steroid hormones have been determined to confirm the inhibitory effects of polyphenols on 3β-HSD and aromatase. Accordingly, we tested the effects of polyphenols on steroidogenic pathways by simultaneously measuring levels of nine steroid hormones.…”

Section: Discussionmentioning

confidence: 99%

“…These inhibitory effects were in good agreement with the results of previous studies. [9][10][11] Daidzein carries a hydroxyl group at C7 of the A-ring and competes with 3β-HSD substrates because of its steric structure and strong electron affinity with the active center of 3β-HSD. 9) Genistein, apigenin, hesperetin, naringenin, and eriodictyol also carry a hydroxyl group at C7 of the A-ring, suggesting that their inhibitory mechanisms are similar to those of daidzein.…”

Section: Discussionmentioning

confidence: 99%

“…For example, daidzein, genistein, apigenin, and naringenin inhibit 3β-hydroxysteroid dehydrogenase (3β-HSD). [9][10][11] while daidzein and genistein inhibit cytochrome P450 (CYP) 21.…”

mentioning

confidence: 99%

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Effect of Polyphenols on Production of Steroid Hormones from Human Adrenocortical NCI-H295R Cells

Hasegawa

Nakagawa

Sato

et al. 2013

Biological & Pharmaceutical Bulletin

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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.Key words apigenin; cytochrome P450 (CYP)17; CYP21; pregnenolone; 17α-hydroxyprogesterone; polyphenol Steroid hormones are secreted by the adrenal cortex and play pivotal roles in stress response, immune response, antiinflammatory actions, carbohydrate metabolism, protein catabolism, and electrolyte homeostasis.1) Disrupting the secretion of these hormones has a serious impact on human health. For example, in Cushing's syndrome, hyperproduction of cortisol results in redistribution of fat to the face (moon face), hypertension, central obesity, and striae distensae. In cases of aldosteronism, hyperproduction of aldosterone induces renal reabsorption of sodium and water, which leads to a rise in circulating blood volume and hypertension. In addition, under stressful conditions, such as those related to deteriorating socioeconomic situations, chronic work-related stress, anxiety, and depression, the neuroendocrine response is upregulated, and the resulting cortisol hyperproduction triggers insulin resistance. Furthermore, the hypothalamic-pituitary-adrenal axis is hyperactivated under chronic stress, which in turn induces abdominal obesity, thereby leading to metabolic syndrome. 2)Agents and supplements that modulate steroid hormone levels play pivotal roles in treating the above diseases and conditions. Several food constituents have already been reported as steroid hormone inhibitors. For example, water-soluble l...

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Section: Genistein (G) Apigenin (A) Hesperetin (H) Naringenin (N)mentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…For example, daidzein, genistein, apigenin, and naringenin inhibit 3β-hydroxysteroid dehydrogenase (3β-HSD). [9][10][11] while daidzein and genistein inhibit cytochrome P450 (CYP) 21.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Effect of Polyphenols on Production of Steroid Hormones from Human Adrenocortical NCI-H295R Cells

Hasegawa

Nakagawa

Sato

et al. 2013

Biological & Pharmaceutical Bulletin

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show abstract

“…Urea derivatives (5a, 5c-5g) have enzyme inhibitory effect due to HOMO-LUMO energy differences. Generally, differentiation between HOMO and LUMO reflects the intensity of electron affinity, and lower differentiation suggests higher electron affinity 35 . The calculated HOMO-LUMO energy differences of the compounds((5a, 5c-5g) showed a linear relationship for higher inhibitory effects with increasing ΔE HOMO-LUMO values which are higher than 0.23eV and the compounds (5b, 5h-5k) which have ΔE HOMO-LUMO values lower than 0.23eV showed enzyme activity effects.…”

Section: Resultsmentioning

confidence: 99%