Endocrinology and Metabolism

Original Articles

Estrogen Receptor Gene Polymorphism, Urinary Estrogen Metabolites and Bone Mineral Density in Korean Postmenopausal Women.: Ji Hyun Lee, Sung Kil Lim, Young Jun Won, Seok Ho Kwon, Bong Soo Cha, Young Duk Song, Hyun Chul Lee, Kap Bum Huh; J Korean Endocr Soc. 1996;11(4):468-478. Published online November 7, 2019

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Abstract PDF: Background
Estrogen status is important for maintaining the homeostasis of bone. Estrogen has direct effects on bone cells, through binding to the high-affinity estrogen receptor. Several recent studies suggest that there might be genetically determined variations in biosynthesis and function of estrogen receptor in postmenopausal osteoporosis. Also the main cause of postmenopausal osteoporosis is decreased level of serum estrogen, whereas there had been some suggestion that the remaining estrogen have some effect on bone metabolism after menopause. We investigated the relationship between estrogen receptor gene PvulI polymorphism and bone mineral density(BMD), and the relationship between 18 urinary metabolites of estrogen and BMD in Korean postmeno- pausal osteoporosis. Methods: We examined the PvuII polymorphism of the estrogen receptor gene in 5' upstream region and the first intron by restrietion frapnent length polymorphism analysis in 62 postmeno- pausal wornen, BMD was measured by DEXA. The urinary estrogen metabolites were determined by GC/MS(Gas Chromatography-Mass Spectrometry) at Korean Institute of Science and Techno- logy Doping Control Center. Results: BMD of the spine and the femoral neck correlated with body weight, height, body mass index as we expected. There was no polymorphism of PvuII restriction site on 5 upstream region of estrogen receptor gene. Whereas the prevalen~ee of the PP, Pp, pp genotype in the first intron of estrogen receptor was 12.9%, 45.2%, 41.9%, respectively. But, there was no correlation between PvuII genotype and the spinel and femoral neck BMD. 2(OH)E2 among 18 urinary metabolites of estrogen, showed a negative correlation with the spinal and femoral neck BMD(r =-0.2551, p<0.05, and r =-0.3341, p<0.01, respectively), and the ratio of 16a(OH)E2/2(OH)E1> revealed a positive correlation with the spinal BMD(r =0.3057, p<0.05). In stepwise multiple regression analysis, body weight, 2(OH)E2, 16a(OH)E1, 2(Meo)E1 were independent predictors of the spinal bone density, and body weight and 2(OH)E2 were independent predictors of the femoral neck bone density. Conclusion: These results suggested that restrietion fragment length polymorphism analysis of the estrogen receptor gene with PvuII restriction enzyme was not helpful for early detection of patients at risk of developing osteoporosis. However, the ratio of 16-hydroxylation to 2-hydroxylation of estrogen metabolism was reduced in postmenopausal women and high catecholestrogen formation might be a greater risk factor for osteoporosis.

Endocrine Research
The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes: Cheol Ryong Ku, Yoon Hee Cho, Zhen-Yu Hong, Ha Lee, Sue Ji Lee, Seung-soo Hong, Eun Jig Lee; Endocrinol Metab. 2016;31(2):328-335. Published online April 8, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.328

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Abstract PDF PubReader

Background

Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes.

Methods

For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments.

Results

RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group.

Conclusion

RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters.

Citations

Citations to this article as recorded by

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Transcriptional Regulation of the Estrogen Receptor alpha Gene by Testosterone in Cultures of Primary Rat Sertoli Cells.: Sang Kuk Yang, Kyung Ah Yoon, Eun Jin Yun, Kyoung Sub Song, Jong Seok Kim, Young Rae Kim, Jong Il Park, Seung Kiel Park, Byung Doo Hwang, Kyu Lim; J Korean Endocr Soc. 2006;21(2):106-115. Published online April 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.2.106

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Abstract PDF: BACKGROUND
We wanted to identify the presence of the estrogen receptor (ER) alpha in Sertoli cells and gain insight on the regulation of the ER alpha gene expression by testosterone in Sertoli cells. The transcriptional regulation of the ER alpha gene was investigated in primary Sertoli cell cultures by in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR). METHODS: Primary Sertoli cell culture was performed. The expression levels of ER alpha and ER beta mRNA in Sertoli cells were detected by Northern blot, RT-PCR, immunocytochemistry and in situ hybridization. RESULTS: The ovary, testis and epididymis showed a moderate to high expression of ER alpha while the prostate, ovary and LNCap cells showed the ER beta expression. ER alpha mRNA and protein were detected in the germ cells and Sertoli cells by in situ hybridization and immunocytochemistry. The level of ER alpha mRNA was gradually decreased in a time-dependent manner after testosterone treatment, and the changes of ER alpha mRNA were dependent on the concentration of testosterone. Androgen binding protein and testosterone-repressive prostate message-2 (TRPM-2) mRNA were reduced at 24 hour by estradiol, while the transferrin mRNA was not affected. ER alpha mRNA was strongly detectable in the testes of 7 days-old-rats, but it was gradually decreased from 14 to 21 days of age. The primary Sertoli cells also showed the same pattern. The ER alpha gene expression was also regulated by testosterone in the Sertoli cells prepared from the 14- and 21-day old rats. CONCLUSIONS: These results suggest that ER alpha is transcriptionally regulated by testosterone and it may play some role in the Sertoli cells.

Association Between Peak Bone Mass and Genetic Polymorphisms of the Vitamin D Receptor, Estrogen Receptor, and Type I Collagen 1 Genes in Healthy Young Korean Women.: Hong Kyu Kim, Sang Wook Kim, Eun Sook Kim, Ghi Su Kim; J Korean Endocr Soc. 2001;16(1):97-114. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Genetic suggest that strongest effect is observed in the premenopausal peak bone mass, which become less with age. However, the evaluation of candidate genes polymorphisms has been most frequently done in postmenopausal women and the results have been controversial. Therefore, we studied the possible association of the peak bone mass and candidate for osteoporosis genes polymorphism in premenopausal women. METHODS: The associations between BMD and polymorphisms of the vitamin D receptor (3'-end region by BsmI restriction enzyme and start codon by FokI restriction enzyme), estrogen receptor (by PvuII and XbaI restriction enzyme), and type I collagen 1 (Sp1 binding site by MscI and BalI restriction enzyme) genes were examined in 100 healthy young Korean women who had a peak bone mass (age 20-35 years). Bone mineral densities were measured by dual energy X-ray absorptiometry (DEXA). Dietary calcium intake was also measured using a food frequency questionnaire. RESULTS: The frequencies of the B allele of the vitamin D receptor gene BsmI polymorphism and the X allele in the estrogen receptor gene, XbaI polymorphisms were lower in Koreans than those in Caucasians. The allelic frequencies of the vitamin vitamin D receptor gene FokI polymorphism and the estrogen receptor gene PvuII polymorphism were similar to those of Caucasians. No significant association was found between BMD and the vitamin D receptor genotype according to BsmI or FokI polymorphisms. There was also no significant relation between the PvuII or XbaI polymorphisms of the estrogen receptor gene and BMD. The associations between BMD and cross-genotypes combining the vitamin D receptor gene (BsmI and FokI) and estrogen receptor gene (PvuII and XbaI) polymorphisms were also analyzed. Among the subjects who lacked the Bf haplotype of the vitamin D receptor gene, the BMD of the femoral neck area was significantly higher in subjects lacking Px haplotypes of the estrogen receptor gene than in those having Px haplotype (p < 0.05). When dietary calcium intake was taken into consideration, there were significant differences in BMD according to the cross-genotype in the group having a low calcium intake (< 500 mg/day). The subjects that lacked the Bf and Px haplotypes had a significantly higher BMD in the femoral neck (p < 0.01), Ward's triangle (p < 0.05), and in the trochanteric area (p < 0.05) than those who lacked Bf but a Px haplotype. We did not find a polymorphism in the Sp1 binding site of the type I collagen 1 gene in our subjects. CONCLUSION: These data suggest that a complex interaction of vitamin D and the estrogen receptor gene with the dietary calcium intake, rather than a polymorphism of a single gene, may influence peak bone mass in healthy young Korean women.

Association of Estrogen Receptor Genotypes with Serum Lipids and Responsiveness of Serum Lipids to Hormonal Replacement Therapy in Korean Postmenopausal Women.: So Ra Park, Jae Eun Park, Chung Kyu Hwang, Phil Ho Jung, Chang Hoon Yim, Ho Yeon Chung, Ki Ok Han, Hyun Ku Yoon, Hak Chul Jang, In Kwon Han; J Korean Endocr Soc. 1999;14(3):553-561. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Several biologically plausible mechanisms have been proposed for estrogen-mediated caridoprotection, including estrogen-assocaited changes in lipid metabolism and endothelial function of vessel walls. These effects are thought to be mediated via estrogen receptor (ER). Relationships between ER polymorphisms and serum lipid levels were not investigated enoughly. METHODS: Three restriction fragment length polymorphisms (RFLPs) at the ER gene locus, represented as B-variant, PvuII and XbaI, and their relationship to serum lipid levels were examined in 318 postmenopausal women. Their mean age was 54.5+/-6.5 years (mean+SD). An association between ER genotypes and changes in lipid levels after 1 year of estrogen replacement therapy was also investigated in follow-up 251 women. RESULTS: The B-variant was not found in Korean women. The distribution of the PvuII and XbaI polymorphisms was as follows: PP 109 (34%), Pp 166 (52%), pp 43 (14%), and XX 204 (64%), Xx 95 (30%), xx 19 (6%). Significant relationship was found between genotypes and changes in serum total cholesterol levels after lyr estrogen replacement therapy. There was no significant relationship between ER genotypes and changes in HDL cholesterol, LDL cholesterol and triglyceride levels after estrogen therapy. CONCLUSION: These data indicate that these polymorphisms are possible predictor on lipid response to estrogen replacement therapy.

Regulation of Estrogen Receptor mRNA in Rat Anterior Pituitary Gland.: Min Seok Chun, Duck Bae Park, Yong Bin Park, Kyung Yoon Kam, Chang Mi Kim, Kyung Ja Yoo; J Korean Endocr Soc. 1997;12(4):518-527. Published online January 1, 2001

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Abstract PDF: The estrogen receptor (ER) is present in a wide variety of mammalian tissues and is required for the physiological responses of estrogen, including estrogen-induced tissue-specific changes in gene expression. But most of our knowledge on the regulation of ER mRNA levels comes from in vivo steroid replacement experiments or cancer cell lines that express the ER. Thus the present study was attempted to determine 1) the anterior pituitary ER mRNA levels during rat estrous cycle 2) if estradiol itself directly modulates the ER mRNA levels in cultured rat anterior pituitary using RT-PCR method. In rats with 4 day estrous cycle, the ER mRNA levels in anterior pituitary gland reached to maximum at proestrus 11:00h just before serum estradiol concentration showed the highest. From then, the ER mRNA levels gradually declined during the rest of the proestrus. On the other hands, in cultured rat anterior pituitary cells, the ER mRNA levels were significantly decreased by the treatment of estradiol. These results indicate that the surge of estradiol was proceeded by the increase in pituitary ER mRNA levels during the proestrus and in cultured anterior pituitary cells, estrogen might be involved in the down-regulation of the ER mRNA levels.

Non-association of Pvull and Xval Estrogen receptor Genotypes with Bone Mineral Density and Bone Markers in Korean Premenopausal Women.: Hyun Koo Yoon, Ho Yeon Chung, In Gul Moon, Chang Hoon Yim, Sang Woo Kim, Ki Ok Han, In Kwon Han, Hun Ki Min, Dong Won Suh, Dong Hee Cho, Bo Kyung Park, Jong Tae Choi; J Korean Endocr Soc. 1997;12(2):207-214. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Bone mineral density (BMD) is under strong genetic control. A recently reported case of severe estrogen resistance caused by a germ-line mutation at the estrogen receptor gene locus suggests the possibility that other variants of the estrogen receptor (ER) gene could be responsible for the heritable components of bone density. METHODS: Two restriction fragment length polymorphisms (RFLPs) at the ER gene locus, represented as PvuII and XbaI, and their relationship to bone mineral density (BMD) and bone turnover markers were examined in 95 healthy premenopausal women. Their mean age was 29 +-6.9 years (mean+-SD). RESULTS: The distribution of the PvuII and XbaI RFLPs was as follows: PP 20 (21.1%), Pp 40 (42.1%), pp 35 (36.8%), and XX 5 (5.3%), Xx 33 (34.7%), xx 57 (60.0%) (capital letters signify the absence of, and lower case letters signify the presence of the restriction site of each RFLP). There was no significant relation between ER genotypes and BMD measured at several sites such as lumbar spine (L2-4), distal forearm, and femoral neck. Also no significant genotypic differences were found in the several biochemical markers and sex hormone status. CONCLUSION: These data indicate that these polymorphisms are not predietive of bone turnover nor BMD in a sample of healthy Korean premenopausal women.

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