Steroid and Phyto-Oestrogen Binding to Sheep Uterine Receptors in Vitro

Abstract

The binding affinities and receptor specificity of sheep uterine cytosol for steroid oestrogens and also for weak plant oestrogens of the isoflavone and coumestan groups and some synthetic compounds were studied. The binding affinities of the weak oestrogens fall within a range which has usually been neglected. Relative molar binding (RMB) affinities for the steroid oestrogens confirmed the importance of the phenolic 3-hydroxyl group and the influence of substitutions at C-16 and C-17, as seen with uterine cytosols from other species. Relative molar binding affinities were very much lower when the oestrogens were present as sulphate esters, glucosiduronate and methyl ether derivatives; acetates showed similar RMB affinities to their parent compounds. Phyto-oestrogens were found to compete with oestradiol for binding sites. Coumestrol and miroestrol had the highest RMB affinities of about 5 (oestradiol-17\g=b\ = 100) when incubated at 25 \ s=deg\ C, and values for genistein, equol, daidzein and O-desmethylangolensin lay between 1 and 0\m=.\05.The mono-methoxy compounds, biochanin A, formononetin and 4\m=' \-methoxy\x=req-\ coumestrol had RMB affinities of less than 0\m=.\01.Incubation at 37, 25 and 4 \ s=deg\ Cshowed that RMB affinities were greater at the lower temperatures.Relative molar binding affinities of the phyto-oestrogens in vitro compared with their oestrogenic potencies in vivo showed that the ranking of most of the compounds by these two criteria was similar. Structure-activity correlations were deduced from the results. A similar relationship of RMB affinity to biological potency was also noted for the steroid oestrogens and a homologous series of stilbenediols. The results obtained are relevant to competitive protein-binding analyses and to the mechanism of action of oestrogens and phyto-oestrogens.

Metabolism of Soyasaponin I by Human Intestinal Microflora and Its Estrogenic and Cytotoxic Effects

“…Soyasaponin I more potently induced PR protein, which is an endogenous estrogen responsive gene, than soyasapogenol (data not shown). Beck et al (2005) and Shutt and Cox (1972) reported that the isoflavones, genistin, genistein, and daidzein, activated ER-mediated transcription, without direct receptor interaction. However, soyasapogenol B exhibited potent cytotoxicity against various tumor cells, such as HepG2, A549, HeLa and MCF7 cells, although its glycoside soyasaponin I barely showed any cytotoxicity.…”

Nutritional flavonoids impact on nuclear and extranuclear estrogen receptor activities

“…Although the affinity of flavonoids for the both ERα and ERβ (as their aglycone forms) is lower than that of E2, competition binding studies performed by several authors confirmed that genistein, coumestrol, daidzein, and equol showed a distinct preference for ERβ (Table 2; Shutt and Cox, 1972;Davis et al, 1998;Kuiper et al, 1998;Mueller et al, 2004;Escande et al, 2006). In comparison with genistein, 8-prenylnaringenin, a prenylated chalcone that occurs only in the hop plant, was found to be a 100 times more potent ERα agonist but a much weaker agonist of ERβ in the estradiolcompetition assay for receptor binding (Stevens and Page, 2004).…”

Hormonal and metabolic effects of genistein and daidzein in male rat

“…The consumption of clover caused reproductive disorder or even permanent infertility. It was found that this effect was evoked by genistein, daidzein and their precursors in clover (Shutt and Cox, 1972). In cheetah population isoflavones present in the diet had also a major role in the decline of fertility (Setchell et al, 1987).…”