Effects of phytoestrogens on aromatase, 3β and 17β-hydroxysteroid dehydrogenase activities and human breast cancer cells

Bail, Jean-Christophe Le; Champavier, Yves; Chulia, Albert J.; Habrioux, G

doi:10.1016/s0024-3205(00)00435-5

Cited by 193 publications

(146 citation statements)

References 25 publications

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“…Several studies have addressed the ability of other subclasses of phytochemicals to decrease the activity of a variety of steroidogenic enzymes, including P450scc, P450c17, P450c21, P45011b, 3b-HSD [34][35][36][37][38], aromatase and 17b-HSD [35,38], and affect testosterone production [39,40]. Additionally, EGCG has been shown to inhibit ovarian aromatase activity [5] and estradiol and progesterone production by swine granulosa cells [41].…”

Section: Discussionmentioning

confidence: 99%

Green tea polyphenols inhibit testosterone production in rat Leydig cells

Figueiroa¹,

Vieira²,

Leite³

et al. 2009

Asian J Androl

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This study investigated the acute effects of green tea extract (GTE) and its polyphenol constituents, (−)-epigallocatechin-3-gallate (EGCG) and (−)-epicatechin (EC), on basal and stimulated testosterone production by rat Leydig cells in vitro. Leydig cells purified in a Percoll gradient were incubated for 3 h with GTE, EGCG or EC and the testosterone precursor androstenedione, in the presence or absence of either protein kinase A (PKA) or protein kinase C (PKC) activators. The reversibility of the effect was studied by pretreating cells for 15 min with GTE or EGCG, allowing them to recover for 1 h and challenging them for 2 h with human chorionic gonadotropin (hCG), luteinizing hormone releasing hormone (LHRH), 22(R)-hydroxycholesterol or androstenedione. GTE and EGCG, but not EC, inhibited both basal and kinase-stimulated testosterone production. Under the pretreatment conditions, the inhibitory effect of the higher concentration of GTE/EGCG on hCG/LHRH-stimulated or 22(R)-hydroxycholesterol-induced testosterone production was maintained, whereas androstenedione-supported testosterone production returned to control levels. At the lower concentration of GTE/EGCG, the inhibitory effect of these polyphenols on 22(R)-hydroxycholesterol-supported testosterone production was reversed. The inhibitory effects of GTE may be explained by the action of its principal component, EGCG, and the presence of a gallate group in its structure seems important for its high efficacy in inhibiting testosterone production. The mechanisms underlying the effects of GTE and EGCG involve the inhibition of the PKA/PKC signalling pathways, as well as the inhibition of P450 side-chain cleavage enzyme and 17b-hydroxysteroid dehydrogenase function.

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Section: Discussionmentioning

confidence: 99%

Green tea polyphenols inhibit testosterone production in rat Leydig cells

Figueiroa¹,

Vieira²,

Leite³

et al. 2009

Asian J Androl

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“…Overall, the isoflavones have weak inhibitory activity on aromatase in both cell-free and whole-cell preparations (Le Bail et al 2000, Lacey et al 2005, although Almstrup et al (2002) reported that formononetin, biochanin A, and extract of red clover flowers inhibited aromatase activity at low concentrations (!1 mM) but had oestrogenic activity at higher doses. In contrast, genistein has been reported to increase the aromatase activity in H295R cells and isolated rat follicles (Sanderson et al 2004, Myllymäki et al 2005, and this was paralleled by an increase in promoter-specific aromatase transcripts (Sanderson et al 2004).…”

Section: Phytoestrogens and Aromatasementioning

confidence: 99%

“…In both cell-free preparations and T47-D breast cancer cells, genistein and daidzein inhibited the conversion of oestrone to oestradiol between 1 and 10 mM with weaker or no effects of biochanin A (Mäkelä et al 1995, Le Bail et al 2000, Brooks & Thompson 2005, whilst in human granulosa luteal cells only high doses of genistein (R10 mM), but not biochanin A, inhibited 17b-HSD type 1 (Whitehead & Lacey 2003). This contrasts the relatively potent effects of biochanin A on recombinant 17b-HSD type 5 that reduces androstenedione to testosterone (Krazeisen et al 2001).…”

Section: Phytoestrogens and 17b-hsdsmentioning

confidence: 99%

Phytoestrogens and breast cancer –promoters or protectors?

Rice¹,

Whitehead²

2006

Endocr Relat Cancer

165

119

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The majority of breast cancers are oestrogen dependent and in postmenopausal women the supply of oestrogens in breast tissue is derived from the peripheral conversion of circulating androgens. There is, however, a paradox concerning the epidemiology of breast cancer and the dietary intake of phytoestrogens that bind weakly to oestrogen receptors and initiate oestrogendependent transcription. In Eastern countries, such as Japan, the incidence of breast cancer is approximately one-third that of Western countries whilst their high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have oestrogenic effects. Indeed, their weak oestrogenicity has been used to advantage by herbalist medicine to promote soy products as a natural alternative to conventional hormone replacement therapy (HRT). Such usage could increase in light of recent evidence that long-term HRT usage may be associated with an increased risk of breast cancer with a consequent reduction in prescription rates. So, are phytoestrogens safe as a natural alternative to HRT and could they be promoters or protectors of breast cancer? If they are promoters, then we must assume that it is due to their oestrogenic effect. If they are protectors, then other actions of phytoestrogens, including their ability to inhibit enzymes that are responsible for converting androgens and weak oestrogens into oestradiol, must be considered. This paper addresses these questions by reviewing the actions of phytoestrogens on oestrogen receptors and key enzymes that convert androgens to oestrogens in relation to the growth of breast cancer cells. In addition, it compares the experimental and epidemiological evidence pertinent to the potential beneficial or harmful effects of phytoestrogens in relation to the incidence/progression of breast cancer and their efficacy as natural alternatives to conventional HRT.

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Section: Introductionmentioning

confidence: 99%

“…Type 1 is expressed in the placenta [10] and type 2 is expressed in the testis [11]. Previously, Le Bail et al [10] reported that genistein was a potent inhibitor of placental 3β-HSD1 isoform. In the present study, we evaluated the effects of two isoflavones (genistein and equol) on testicular 3β-HSD and 17β-HSD3 enzyme activity, using microsomal protein fractions obtained from human and rat testes.…”

Section: Introductionmentioning

confidence: 99%

Effects of genistein and equol on human and rat testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 activities

Zhao²,

Chu³

et al. 2010

Asian J Androl

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The objective of the present study was to investigate the effects of genistein and equol on 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) in human and rat testis microsomes. These enzymes (3β-HSD and 17β-HSD3), along with two others (cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17α-hydroxylase/17-20 lyase), catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3β-HSD activity (0.2 µmol L -1 pregnenolone) with half-maximal inhibition or a half-maximal inhibitory concentration (IC 50 ) of 87 ± 15 (human) and 636 ± 155 nmol L -1 (rat). Genistein's mode of action on 3β-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD + . There was no difference in genistein's potency of 3β-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3β-HSD, genistein had lesser effects on human and rat 17β-HSD3 (0.1 µmol L -1 androstenedione), with an IC 50 ≥ 100 µmol L -1. On the other hand, equol only inhibited human 3β-HSD by 42%, and had no effect on 3β-HSD and 17β-HSD3 in rat tissues. These observations imply that the ability of soy isoflavones to regulate androgen biosynthesis in Leydig cells is due in part to action on Leydig cell 3β-HSD activity. Given the increasing intake of soy-based food products and their potential effect on blood androgen levels, these findings are greatly relevant to public health.

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Effects of phytoestrogens on aromatase, 3β and 17β-hydroxysteroid dehydrogenase activities and human breast cancer cells

Cited by 193 publications

References 25 publications

Green tea polyphenols inhibit testosterone production in rat Leydig cells

Green tea polyphenols inhibit testosterone production in rat Leydig cells

Phytoestrogens and breast cancer –promoters or protectors?

Effects of genistein and equol on human and rat testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 activities

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