• Journal of Ginseng Research
• /
• v.41 no.2
• /
• pp.215-221
• /
• 2017

Ginseng has been used in China for at least two millennia and is now popular in over 35 countries. It is one of the world's popular herbs for complementary and alternative medicine and has been shown to have helpful effects on cognition and blood circulation, as well as anti-aging, anti-cancer, and anti-diabetic effects, among many others. The pharmacological activities of ginseng are dependent mainly on ginsenosides. Ginsenosides have a cholesterol-like four trans-ring steroid skeleton with a variety of sugar moieties. Nuclear receptors are one of the most important molecular targets of ginseng, and reports have shown that members of the nuclear receptor superfamily are regulated by a variety of ginsenosides. Here, we review the published literature on the effects of ginseng and its constituents on two main sex steroid hormone receptors: estrogen and androgen receptors. Furthermore, we discuss applications for sex steroid hormone receptor modulation and their therapeutic efficacy.

• Proceedings of the Ginseng society Conference
• /
• 1993.09a
• /
• pp.127-131
• /
• 1993

The effects of total ginseng saponin. extracts of Panax ginseng C.A. Meyer, on the differentiation of F9 teratocarcinoma stem cells were studied. F9 stem cells cultured in the presence of ginseng saponin together with dibutyric cAMP became parietal endoderm - like cells. Moreover, the expressions of differentiation marker genes. laminin. type IV collagen. and retinoic acid $receptor-{\beta}(RAR{\beta})$ were increased after treatment of ginseng saponin. Among various ginsenosides purified from crude ginseng saponin, $Rh_1\;and\;Rh_2$ caused the differentiation of F9 cells most effectively. Since ginsenosides and steroid hormone show resemblance in chemical structure. we studied the possibility of the involvement of a steroid receptor in the differentiation process induced by ginsenosides. According to Southwestern blot analysis, a 94 kDa protein regarding as a steroid receptor was detected in F9 cells cultured in the medium containing ginseng saponin. Based on these data, we suggest that ginseng saponin, especially ginsenosides $Rh_1\;and\;Rh_2$ cause the differentiation of F9 cells and the effects of ginsenosides might be exerted via binding with a steroid receptor or its analogous nuclear receptor.

• Toxicological Research
• /
• v.17 no.1
• /
• pp.65-71
• /
• 2001

The key targets of endocrine disruptors are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. A yeast-based steroid hormone receptor gene trascription assay was previously developed for the evaluation of chemicals with endocrine modulating activity. The yeast transformants used in this assay contain the human estrogen receptor along with the appropriate steroid response elements upstream of the $\beta$-galactosidase reporter gene. We tried to evaluate several natural and synthetic steroids of their potential to interact directly with the steroid receptor. Some putative endocrine disruptors, including nonylphenol, are weakly estrogenic. But the combined treatment oj these chemicals with di-(2-ethylhexyl)phthalate (DEHP) significantly increased the $\beta$-galactosidase activity in the yeast transformant. These results suggest that we also have to consider the synergistic effects of endocrine disruptors. In this study, we showed that yeast-based bioassay is a valuable tool for screening potential endocrine disruptors and quantitative determination of estrogenicity. And the possibility that the estrogen receptor binds multiple environmental chemicals adds another level of complexity to the interaction between the endocrine disruptors and the human hormone system.

• Journal of Ginseng Research
• /
• v.27 no.3
• /
• pp.93-97
• /
• 2003

Alternative or complementary medicine plays an important role in health care system. Ginseng, being one of the most popular oriental herbs, is believed to contain various steroid hormone activity. Ginseng has been demonstrated pharmacological effect in the cardiovascular, endocrine, central nervous, and immune system. Our objective was to study that total saponin might mediate some of their actions by binding to the steroid hormone receptor, as they share many of the actions of steroid hormone in various physiological system. Using total saponin from Panax Ginseng, we have studied the possibility of total saponin being a potential estrogen receptor, androgen receptor, and retinoic acid receptor ligand. Total saponin activated the transcription of both the estrogen and androgen responsive luciferase reporter plasmids at a concentration of 100$\mu\textrm{g}$/ml in COS cells transiently transfected with the corresponding receptor and hormone responsive receptor plasmids. And total saponin caused a concentration-dependent stimulation of estrogen receptor. Total saponin increased the expression of estrogen responsive c-fos proto-oncogene at the protein level in MCF7 cells at 24 h treatment as examined by Western analysis. The c-fos induction was used as a specific marker of estrogen responsiveness. This activation was inhibited by the specific estrogen receptor antagonist, ICI 182,780. However, total saponin failed to activate the retinoic acid receptor in COS cells transiently transfected with the corresponding receptor and retinoic acid responsive reporter plasmids. These results show that total saponin is capable of activating estrogen and androgen receptors.

• Toxicological Research
• /
• v.22 no.1
• /
• pp.15-22
• /
• 2006

Many of endocrine disrupting chemicals induce effects via interaction with hormone receptors and responsive elements in target cells. We investigated endocrine disrupting effects of some food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD and PCBs in yeast transformants expressing human steroid hormone receptors along with steroid responsive elements. The response limit of genetically recombinant yeast to $17{\beta}$-estradiol, testosterone and progesterone was $1{\times}10^{-16},\;1{\times}10^{-12}\;and\;1{\times}10^{-13}M$, respectively. BHT induced weak transcriptional activity in estrogen sensitive yeast, while BHA and sorbic acid interacted weakly with androgen receptor/responsive element. CPM induced transcriptional activities in all types of yeasts sensitive to steroid hormones. Zearalenone and genistein induced high transcriptional activation in estrogen sensitive yeast with relative potencies almost $10^8$ folds lower than $17{\beta}$-estradiol. TCDD induced transcriptional activation weakly in estrogen- and progesterone- sensitive yeasts. This study elucidated that recombinant yeast is a sensitive and high-throughput system and can be used for the direct assessment on chemical interactions with steroid receptors and responsive elements. Also, the present study raises the requirement of evaluation on the endocrine disrupting effects of BHT, BHA, sorbic acid, CPM and TCDD for their transcription activity in yeast screening system though weak in intensity.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1999.04a
• /
• pp.5-8
• /
• 1999

여성의 breast cancer의 1/3 의 경우가 hormone-dependent에 의한 것이다. 따라서 그 치료의 접근 방법으로써 estrogen receptor에 작용하거나, receptor-mediated gene trenscription을 저해하는 antiestrogen을 사용하는 것이 있다. Estrogen은 microsomal cytochrome P-450 enzyme complex system에 의해 androgen으로부터 생합성되는 hormone이며, estrogen product는 steroid product의 biosynthetic sequence의 마지막 단계에서 생산되고, aromatase는 이에 관여하는 enzyme으로써, aromatase를 선택적으로 저해하는 경우에 다른 steroid의 생산에 영향을 미치지 않고 estrogen 생산을 감소 시킬 수 있다. 이러한 관점에서, aromatase를 선택적으로 저해하는 것은 hormone-dependent breast cancer를 완화시킬 수 있는 가능성을 가진 cancer chernopreventive agents의 새로운 방법이라 할 수 있다.

• Journal of Plant Biotechnology
• /
• v.42 no.4
• /
• pp.277-283
• /
• 2015

Plant genome analyses, including Arabidopsis thaliana showed a large gene family of plant receptor kinases with various extracellular ligand-binding domain. Now intensively studies to understand physiological and cellular functions for higher plant receptor kinases in diverse and complex biological processes including plant growth, development, ligands perception including steroid hormone and plant-microbe interactions. Brassinosteroids (BRs) as a one of well know steroid hormone are plant growth hormones that control biomass accumulation and also tolerance to many biotic and abiotic stress conditions and hence are of relevance to agriculture. BRI1 receptor kinase, which is localized in plasma membrane in the cell sense BRs and it bind to a receptor protein known as BRASSINOSTEROID INSENSITIVE 1 (BRI1). Recently, we reported that BRI1 and its co-receptor, BRI1-ASSOCIATED KINASE (BAK1) autophosphorylated on tyrosine residue (s) in vitro and in vivo and thus are dual-specificity kinases. Other plant receptor kinases are also phosphorylated on tyrosine residue (s). Post-translational modifications (PTMs) can be studied by altering the residue modified by directed mutagenesis to mimic the modified state or to prevent the modification. These approaches are useful to not only characterize the regulatory role of a given modification, but may also provide opportunities for plant improvement.

• Environmental Mutagens and Carcinogens
• /
• v.22 no.3
• /
• pp.175-182
• /
• 2002

Endocrine disruptors (EDs) are the chemicals that affect endocrine systems through activation or inhibition of steroid hormone response. It is necessary to have a good system to evaluate rapidly and accurately endocrine-disrupting activities of suspected chemicals and their degradation products. The key targets of EDs are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. We constructed a co-expression system of Gal4p DNA binding domain (DBD)- ligand binding domain of human estrogen receptor $\alpha$ or $\beta$, and Gal4p transactivation domain (TAD)-co-activator AIB-1, SRC-1 or TIF-2 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of CYC1 promoter and Gal4p binding site (GAL4 upstream activating sequence, GAL4$_{UAS}$). Expression of this reporter gene was dependent on the presence of estrogen or EDs in the culture medium. We found that the two-hybrid system with combination of the hER$\beta$ LBD and co-activator SRC-1 was most effective in the xenoestrogen-dependent induction of reporter activity. The extent of transcriptional activation by those chemicals correlated with their estrogenic activities measured by other assay systems, indicating that this assay system is efficient and reliable for measuring estrogenic activity. The data in this research demonstrated that the yeast detection system using steroid hormone receptor and co-activator is a useful tool for identifying chemicals that interact with steroid receptors.s.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.11b
• /
• pp.167-167
• /
• 2002

Many pesticides possess hormonal activity and have been thus classified as endocrine disruptors. Permethrin, a pyrethroid insecticide has little been characterized to it's hormonal potential. In the present study, effects of neonatal exposure to permethrin on the sex steroid receptor levels and hoxa-10 expression of the uteri were investigated in female mice.(omitted)

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1994.11a
• /
• pp.93-98
• /
• 1994

Most drug discovery has focused in recent years on the development of molecules that either interact with or block receptors, proteins that act as on-off switches for genetic activity, on the surfaces of human cells. Now, we have developed a technology that targets “receptors inside the cell” (intracellular receptors), opening a new and compelling avenue for drug discovery. Our receptor-based small molecule drugs can be catagorized in two ways: 1) receptor agonists, or molecules that activate a receptor; and 2) receptor antagonists, or drugs that inactivate a receptor.