[Lotus]

https://en.wikipedia.org/wiki/Genistein
"Several studies have shown that both ERs and PPARs influenced each other and therefore induce differential effects in a dose-dependent way. The final biological effects of genistein are determined by the balance among these pleiotrophic actions"

https://en.wikipedia.org/wiki/Peroxisome...d_receptor

"The function of PPARs is modified by the precise shape of their ligand-binding domain (see below) induced by ligand binding and by a number of coactivator and corepressor proteins, the presence of which can stimulate or inhibit receptor function, respectively"

so it seems that ER's are co dependent with PPARs or symbiotic. may need to do further research on PPAR's to upregulate ER's availability to phytoestrogens.

more research needed

Hi BN,

Red Clover is beneficial for NBE. If you don't know what PPAR (peroxisome proliferator-activated receptor), you should. (Info supplied below).


red clover extract: a putative source for simultaneous treatment of menopausal disorders and the metabolic syndrome.
Mueller M1, Jungbauer A.
Author information

Abstract
OBJECTIVE:
Currently, red clover extract is used to treat menopausal disorders as an alternative to classic hormone therapy. Several human and animal studies have attributed hypolipidemic, hypoglycemic, or antiatherosclerotic effects to red clover extract or isoflavones. This study was designed to determine the peroxisome proliferator-activated receptor (PPAR) gamma activation by red clover extract.
DESIGN:
The PPARgamma binding affinities and the transactivation activities of red clover extracts, isoflavones, and their metabolites were analyzed. The presence of specific substances in the extracts was proved by high-performance liquid chromatography/electrospray ionization/mass spectrometry.
RESULTS:
The red clover extracts and the compounds genistein and biochanin A were potent PPARgamma ligands and activators. Several metabolites exerted higher binding affinities or transactivational activities than their precursor molecules. 6-Hydroxydaidzein exerted a more than 100-fold higher binding affinity than its precursor daidzein. The maximal transactivational activity of 6-hydroxydaidzein and 3'-hydroxygenistein exceeded even that of rosiglitazone, a known PPARgamma agonist. Equol and O-desmethylangolensin showed an approximately fivefold higher binding affinity and, in the case of O-desmethylangolensin, a fourfold higher PPARgamma agonistic activity than the precursor. The daily dose of Menoflavon forte, a widely used red clover extract for treatment of menopausal disorders, provides theoretically 15% to 30% of the daily recommended dose of rosiglitazone. Considering the more active metabolites formed, activity must be higher in vivo.
CONCLUSIONS:
This study shows that red clover extracts, the major compounds, and especially several main metabolites exert significant PPARgamma binding and transactivational activity. Red clover extract, which is currently used for treating menopausal disorders, could be simultaneously used for ameliorating the metabolic syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/18724264



peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression.
Schoonjans K1, Staels B, Auwerx J.
Author information

Abstract
The three types of peroxisome proliferator-activated receptors (PPAR), termed alpha, delta (or beta), and gamma, belong to the nuclear receptor superfamily. Although peroxisome proliferators, including fibrates and fatty acids, activate the transcriptional activity of these receptors, only prostaglandin J2 derivatives have been identified as natural ligands of the PPAR gamma subtype that also binds thiazolidinedione antidiabetic agents with high affinity. PPARs heterodimerize with retinoic X receptor (RXR) and alter the transcription of target genes after binding to response elements or PPREs, consisting of a direct repeat of the nuclear receptor hexameric DNA recognition motif (PuGGTCA) spaced by 1 nucleotide (DR-1). Upon activation by fatty acids (FAs) and drugs that affect lipid metabolism, PPARs control the expression of genes implicated in intra- and extracellular lipid metabolism, most notably those involved in peroxisomal beta-oxidation. PPARs partially mediate the inductive effects of fibrates and fatty acids on high density lipoprotein (HDL) cholesterol levels by regulating the transcription of the major HDL apolipoproteins, apoA-I and apoA-II. The hypotriglyceridemic action of fibrates and certain fatty acids also involves PPAR and is constituted of: 1) increased hydrolysis of plasma triglycerides due to induction of LPL and reduction of apoC-III expression; 2) stimulation of cellular fatty acid uptake and conversion to acyl-CoA derivatives due to increased expression of genes for fatty acid transport protein and acyl-CoA synthetase; 3) increased peroxisomal and mitochondrial beta-oxidation; and 4) decreased synthesis of fatty acids and triglycerides and decreased production of very low density lipoprotein (VLDL). Hence, both enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL particles contribute to the hypolipidemic effect of fibrates and fatty acids. Finally, PPARs appear to be involved in differentiation processes because activation of PPAR gamma 2 triggers adipocyte differentiation and stimulates expression of several genes critical to adipogenesis. It is suggested that PPARs are key messengers responsible for the translation of nutritional and pharmacological stimuli into changes in gene expression and differentiation pathways.
PMID: 8725145 [PubMed - indexed for MEDLINE] Free full text