Paradoxical interactions among estrogen receptors, estrogens and SERMS: mutual annihilation and synergy

DT56a stimulates gender-specific human cultured bone cells in vitro

“…This phenomenon of mutual annihilation of action between E 2 and a SERM such as tamoxifen, tamoxifen methiodide or raloxifene, was previously described in prepubertal female rat skeletal tissues and cells in culture [22,23].…”

Estrogenic activity of glabridin and glabrene from licorice roots on human osteoblasts and prepubertal rat skeletal tissues

“…Additionally, glabridin like raloxifene behaves like a SERM (Fig. 4), exhibiting the phenomenon of mutual annihilation [24], namely, inhibiting each other activity as well as E 2 activity, which has been suggested to result from the formation of mixed heterodimers of ligand-ER(s) monomers. The high degree of conformational specificity of this interaction is shown in the fact that several other phytoestrogens including genistein and resveratrol [24] do not exhibit this phenomenon.…”

DT56a (Femarelle): A natural selective estrogen receptor modulator (SERM)

“…SERMs can be full agonists when provided alone, but complete antagonists at supra physiological doses in the presence of estrogen [28,29]. When a SERM like tamoxifen, tamoxifen methiodide or raloxifene was given together with E 2 to pre pubertal immature female rats, the effect of those compounds on the induction of CK specific activity in diaphysis, epiphysis and the uterus was antagonized [28]. In the present study, we found that DT56a although active by itself in the different organs, antagonized E 2 activity when applied together, similar to the other SERMs.…”

“…The phenomenon of mutual annihilation of action between estradiol-17␤ (E 2 ) and a selective estrogen receptor modulator such as tamoxifen, tamoxifen methiodide or raloxifene, was previously described in pre pubertal female rat skeletal tissues in culture [28]. This study showed that compounds that activate ER alone, when given together, antagonized each other activity [28,29].…”