• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2003.11a
• /
• pp.117-117
• /
• 2003

PPARs (peroxisome proliferator activated receptors) are member of nuclear hormone receptors superfamily. Activations of PPARs upon binding with ligands modulate glucose metabolite, differentiation of adipocyte, inflammation response, and so on. Thiazolidinedione analog is one of potential antidiabetic drug that binds and activates PPARν selectively and enhances insulin sensitivity. In an effort to develop novel and effective antidiabetic thiazolidindione analogs, syntheses of benzoxazole and benzothiazole-linked thiazolidinedione analogs were performed via coupling reaction of benzoxazolylalkylaminoethanol with hydroxybenzylthiazolidinedione to develop novel and effective antidiabetic thiazolidindiones. All compounds were evaluated their biological potency by PPARν transactivation assay and revealed the similar potency with Troglitazone. However, lengthening of N-alkyl substituent did not seem to be beneficial for the activity.

• Clinical and Experimental Reproductive Medicine
• /
• v.46 no.3
• /
• pp.99-106
• /
• 2019

Bisphenol A (BPA) is an endocrine-disrupting chemical that is capable of interfering with the normal function of the endocrine system in the body. Exposure to this chemical from BPA-containing materials and the environment is associated with deleterious health effects, including male reproductive abnormalities. A search of the literature demonstrated that BPA, as a toxicant, directly affects the cellular oxidative stress response machinery. Because of its hormone-like properties, it can also bind with specific receptors in target cells. Therefore, the tissue-specific effects of BPA mostly depend on its endocrine-disrupting capabilities and the expression of those particular receptors in target cells. Although studies have shown the possible mechanisms of BPA action in various cell types, a clear consensus has yet to be established. In this review, we summarize the mechanisms of BPA action in spermatozoa by compiling existing information in the literature.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.6
• /
• pp.2161-2166
• /
• 2015

Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. The sequence similarities of human $ER{\alpha}$, mouse $ER{\alpha}$, rat $ER{\alpha}$, dog $ER{\alpha}$, and cat $ER{\alpha}$ are above 90%, but structures of $ER{\alpha}$ may different among species. Estrogen can be agonist and antagonist depending on its target organs. This hormone play roles in several diseases including breast cancer. There are variety of the relative binding affinity (RBA) of ER and estrogen species in comparison to $17{\beta}-estradiol$ (E2), which is a natural ligand of both $ER{\alpha}$ and $ER{\beta}$. The RBA of the estrogen species are as following: diethyl stilbestrol (DES) > hexestrol > dienestrol > $17{\beta}-estradiol$ (E2) > 17- estradiol > moxestrol > estriol (E3) >4-OH estradiol > estrone-3-sulfate. Estrogen mimetic drugs, selective estrogen receptor modulators (SERMs), have been used as hormonal therapy for ER positive breast cancer and postmenopausal osteoporosis. In the postgenomic era, in silico models have become effective tools for modern drug discovery. These provide three dimensional structures of many transmembrane receptors and enzymes, which are important targets of de novo drug development. The estimated inhibition constants (Ki) from computational model have been used as a screening procedure before in vitro and in vivo studies.

• Laboraroty Animal Research
• /
• v.34 no.4
• /
• pp.140-146
• /
• 2018

Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.

• International Journal of Oral Biology
• /
• v.44 no.4
• /
• pp.125-129
• /
• 2019

Osteocalcin is the most abundant non-collagenous protein produced in bone. It has traditionally been regarded as a marker of bone turnover and is thought to act in the bone matrix to regulate mineralization. However, emerging knowledge regarding osteocalcin has expanded to include functions in energy metabolism, fertilization, and regulation of cognition. Fully carboxylated osteocalcin binds to hydroxyapatite, thereby modulating bone turnover, whereas undercarboxylated osteocalcin in the circulation binds to osteocalcin-sensing receptors and acts as a hormone that affects multiple physiological aspects. In this review, we summarize the current knowledge regarding the hormonal actions of osteocalcin in various organs and potential cellular downstream signaling pathway that may be involved.

• The Korean Journal of Zoology
• /
• v.38 no.2
• /
• pp.220-229
• /
• 1995

uftraspirocle (usa) gene product (Uspl is a member of the superfamilv of steroid hormone receptors in Drosophila melonogaster which mediate the hormone action by heteromerization with ecdvsone receptor (EcR). Based on the genetic and molecular characterization of usp, it has been proposed that Usp funtions in at least three significant developmental pathway: embrvogenesis, eve morphogenesis, and female reproduction. In this study, the expression patterns of Usp were investigated by immunohistochemistrv in individual tissues from diHernt developmental stases of Drosophila. Usp is localized in the nucleus with ubiquitous distribution throughout development. Usp expression is detected throughout embrvogenesis. Usp is expressed in imaginal and lanral tissues from late third instar 18nra. The expression pattern of Usp is overlapped by those of EcR. Also Usp is expressed in differentiating adult reproductive organs. This result suggests that Usp is not a transcriptional regulatory factor modulating hormonal response during development, but also play some roles in female and male reproduction of Drosophila.

• Korean journal of applied entomology
• /
• v.40 no.2
• /
• pp.155-196
• /
• 2001

Basically insect hormones include ecdysteroids (molting hormone), juvenile hormones, and neurohormones comprising neuropeptides and biogenic amines. This article reviewed their chemical structures and biological functions. The active molting hormone is 20-hydroxyecdysone in most insects but makisterone A in some other insects including the honey bee and several phytophagous hemipterans. Most insects use JH III, but lepidopterans JH I and II. Dipterans also use a different JH, so-called JH $B_3$(JH III bisepoxide) and we still do not know the exact chemical structure of JH utilized in hemipterans. Some other insects use methyl farnesoate or hydroxylated JH III analogues as their juvenile hormone. Most diverse pictures can be found in neurohormones (NH), especially in neuropeptides, in terms of their number and structure. There are more than 200 neuropeptides (NP), classified into more than 30 families, which structures have been identified, and more of them are expected to be reported in the near future, partly due to rapid development in molecular biological techniques and in analytical techniques. More than half of them are involved in controlling activity of visceral muscles. But function (s) of many NPs are not clarified yet, even though their amino acid sequences have been identified. It is partly due to the fact that a single NP may have multiple functions. Another interesting point is their gene structure, having many number of independent, active peptides in one gene, apparently working for similar or totally different functions. NH also includes amines, such as octopamine, dopamine, serotonin, etc. From now on, investigation will be concentrated on identifying their function (s) and receptors, and on possibilities of their utilization as control agents against pest insects.

• 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 Medicine and Life Science
• /
• v.16 no.1
• /
• pp.34-38
• /
• 2019

Hypogonadism is a clinical syndrome that results in hormone deficiency and can be classified as 1) primary caused by the gonadal failure and 2) secondary by the hypothalamus-pituitary gland dysfunction and/or cardiometabolic complications. Recently the presence of thyroid hormone receptors in different testicular cell types was demonstrated, and thus thyroid dysfunctions would be another cause of secondary hypogonadism. Thus, we investigated the effects of perinatal hypothyroidism on hypogonadism in male Sprague-Dawley rats. Perinatal hypothyroidism was induced by daily administration of 0.05% 6-propyl-2-thiouracil (PTU) by tap water from gestation day 15, which were compared with negative control (PTU (-)) group. At postnatal day 28, hypothyroid pups were divided into 2 groups: PTU (+) group - continued PTU treatment and PTU (+/-) group - stopped PTU until postnatal day 49. Body weights, dehydrotesosterone (DHT), and testosterone levels were checked 2 and 3 weeks after grouping. Body weights were significantly decreased in PTU(+) and PTU(+/-) groups compared with PTU (-) group at postnatal day 28. 3 weeks later, PTU (+/-) group significantly gained weight compared with PTU (+) group. DHT and testosterone levels significantly decreased with PTU treatment, but increased 3 weeks after stopping PTU administration. Perinatal PTU-induced hypothyroid hypogonadism was sustained for 2 weeks after stopping PTU administration, but restored gonadal hormone levels 3 weeks after stopping PTU. These results suggest that researchers should design an experiment on hypothyroid hypogonadism based on the estimated period.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.346.1-346.1
• /
• 2002

FXR (farnesoid X-activated receptor) is a member of nuclear steroid hormone receptor superfamily and especially a orphan receptor, which are able to control mevalonate pathway upon activation by binding of the specific ligands. We. have launched our study for development of FXR specific ligands getting on in lead discovery. A promising lead stilbene analog was obtained through the screening of a set of library compounds which was previously targeted for other nuclear receptors. And then synthetic modilication of the lead was perfoumde. In addition. fishing a new pharmacophore was fried by UNITT aearch. which brought new structural features.