The objective of the present study was to investigate the effects of genistein and equol on 3β-hydroxysteroid de- hydrogenase （3β-HSD） and 17β-hydroxysteroid dehydrogenase 3 （17β-HSD3） in human and rat testis ...The objective of the present study was to investigate the effects of genistein and equol on 3β-hydroxysteroid de- hydrogenase （3β-HSD） and 17β-hydroxysteroid dehydrogenase 3 （17β-HSD3） in human and rat testis microsomes. These enzymes （3β-HSD and 17β-HSD3）, along with two others （cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17α-hydroxylase/17-20 lyase）, catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3β-HSD activity （0.2 μmol L^-1 pregnenolone） with half-maximal inhibition or a half-maximal inhibitory concentration （IC50） of 87 ± 15 （human） and 636 ± 155 nmol L^-1 （rat）. Genistein＇s mode of action on 3β-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD＋. There was no difference in genistein＇s potency of 3β-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3β-HSD, genistein had lesser effects on human and rat 17β-HSD3 （0.1 μmol L^-1 androstenedione）, with an IC50 〉 100μmol L^-1. On the other hand, equol only inhibited human 3β-HSD by 42%, and had no effect on 3β-HSD and 17β-HSD3 in rat tissues. These observations imply that the ability of soy isoflavones to regulate androgen biosynthesis in Leydig cells is due in part to action on Leydig cell 3β- HSD activity. Given the increasing intake of soy-based food products and their potential effect on blood androgen levels, these findings are greatly relevant to public health.展开更多
11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and lo...11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and localization of 11β-HSD in rat testis during postnatal development, and the regulation of these genes by luteinizing hormone （LH） and androgens, mRNA and protein levels were analyzed by quantitative real-time-polymerase chain reaction and western blotting, respectively, in testes collected from rats at postnatal day （PND） 7, 14, 21, 35, and 90, and from rats treated with LH, 7α.methyl-19-nortestosterone （MENT） and testosterone at PND 21 and PND 90. Immunohistochemical staining was used to identify the localization of the 11β-HSD in rat testis at PND 7, 14, and 90. We found that 11β-HSD1 expression was restricted to the interstitial areas, and that its levels increased during rat testis development. In contrast, whereas 11β-HSD2 was expressed in both the interstitial areas and seminiferous tubules at PND 7, it was present only in the interstitial areas at PND 90, and its levels declined during testicular development. Moreover, 11β-HSD1 mRNA was induced by LH in both the PND 21 and 90 testes and by MENT at PND 21, whereas 11β-HSD2 mRNA was induced by testosterone and MENT in the PND 21 testis and by LH in the PND 90 testis. In conclusion, our study indicates that the 11β-HSD1 and 11β-HSD2 genes have distinct patterns of spatiotemporal expression and hormonal regulation during postnatal development of the rat testis.展开更多
3β-Hydroxysteroid-△24 reductase （DHCR24） is a multifunctional enzyme that localizes to the endoplasmic reticulum and has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuro...3β-Hydroxysteroid-△24 reductase （DHCR24） is a multifunctional enzyme that localizes to the endoplasmic reticulum and has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuroprotection against apoptosis caused by amyloid β deposition. The present study aimed to construct two recombinant adenoviruses driving DHCR24 expression specifically in neurons. Two SYN1 promoter DNA fragments were obtained from human （h） and rat （r）. Recombinant Ad-r（h）SYN1-DHCR24 was transfected into AD-293, N2A （mouse neuroblastoma）, and MIN6 （mouse pancreatic carcinoma） cells. Western blot analysis showed DHCR24 was specially expressed in 293 and N2A cells, but no specific band was found in MIN6 cells. This demonstrates that the recombinant adenoviruses successfully express DHCR24, and no expression is observed in non-neuronal cells. TUNEL assay results showed apoptosis was inhibited in adenovirus-transfected neurons. Detecting reactive oxygen species by immunoflu- orescence, we found that adenovirus transfection inhibits apoptosis through scavenging excess reactive oxygen species. Our findings show that the recombinant DHCR24 adenoviruses induce neuron-specific DHCR24 expression, and thereby lay the foundation for further studies on DHCR24 gene therapy for Alzheimer＇s disease.展开更多
It has been proposed that 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which activates glucocorticoids, plays a role in chronic inflammatory diseases including metabolic diseases, rheumatoid arthritis, and ul...It has been proposed that 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which activates glucocorticoids, plays a role in chronic inflammatory diseases including metabolic diseases, rheumatoid arthritis, and ulcerative colitis. We have recently reported that the expression of 11β-HSD1 is increased in the gingiva of patients with chronic periodontitis and in that of rats with ligature-induced periodontitis. In this study, to further demonstrate the involvement of 11β-HSD1 in chronic periodontitis, the expression of 11β-HSD1 was investigated in another rat model of experimental periodontitis induced by intragingival injection of lipopolysaccharide from Porphyromonas gingivalis (LPS-PG). Alveolar bone loss was observed two weeks after intragingival injection of LPS-PG. The level of 11β-HSD1 mRNA assessed by real-time reverse transcriptase-polymerase chain reaction was significantly elevated in LPS-PG-induced periodontitis compared with controls. The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids, was not significantly different between control and LPS-PG-induced periodontitis. The expression of 11β-HSD1 was significantly correlated with that of TNF in LPS-PG-induced periodontitis. The increased expression of 11β-HSD1 protein in LPS-PG-induced periodontitis was confirmed by immunohistochemistry using anti-11β-HSD1 antibody. These results further suggest a role for 11β-HSD1 in the pathogenesis of chronic periodontitis.展开更多
Fourteen compounds of azastene and epostane derivatives (from YG101 to YG114) have been studied. Results showed that only YG102 and YG103 wore found to be positive in interceptivo activities, although they were less p...Fourteen compounds of azastene and epostane derivatives (from YG101 to YG114) have been studied. Results showed that only YG102 and YG103 wore found to be positive in interceptivo activities, although they were less potent than their parent compound──azastene. Levels ofprogesterone in plasma were decreased significantly after administrstion or YG102, 103 and 106. Only YG107 possessed an interceptive activity approximately as potent as that of its paront compound──epostane. Epostane is a mixture of its enol and keto forms and the percentage of both forms defends on various condions. Since YG107 exists only in one form, we believe this derivative of epostane might be useful in the future work.展开更多
Objective: To study the effect of glucocorticoid on the promoter of the pre-receptor glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene. Methods: The 1. 2 kb length sequence u...Objective: To study the effect of glucocorticoid on the promoter of the pre-receptor glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene. Methods: The 1. 2 kb length sequence upstream to the transcription start site of the 11β-HSD1 gene was amplified with polymerase chain reaction (PCR) and then was cloned into pBLCAT6 plasmid carrying chloramphenicol acetyltransferase ( CAT) reporter gene. The plasmid pBLCAT6 carrying the promoter and reporter gene was used to transfect HeLa cells to study the regulation of 11β-HSD1 gene expression by glucocorticoids in terms of reporter gene expression. Results: PCR showed that there was a complete alignment of the amplified sequence with the sequence 1. 2 kb upstream to the transcription start site of 11β-HSD1 gene. When cloned into pBLCAT6 plasmid carrying the reporter gene, this part of the promoter is functional in terms of regulation of reporter gene expression upon transfection into HeLa cells. The synthetic glucocorticoid-dexamethasone induced the reporter gene expression in the system described above, which was blocked by glucocorticoid receptor antagonist RU486. Conclusion: Glucocorticoids can modulate the expression of 11β-HSD1 through a mechanism involving activation of GR and interaction of the promoter of 11β-HSD1 gene.展开更多
The Japanese Orthopedic Association proposed a concept called locomotive syndrome (LS) to identify middle-aged and older adults at high risk of requiring health care services because of problems with locomotion-associ...The Japanese Orthopedic Association proposed a concept called locomotive syndrome (LS) to identify middle-aged and older adults at high risk of requiring health care services because of problems with locomotion-associated lower muscle mass. To prevent LS, it is important to increase muscle mass and muscle strength in middle-age by continuous resistance training. A total of 38 men and women were assessed at baseline and 6 months. Body composition, physical strength and salivary cortisol and cortisone were analyzed. The exercise intervention program was performed by individual muscle endurance level. Body weight, muscle weight and basal metabolism were increased after exercise intervention. The 30-second sit-up test and 3-minute walking were increased, and the 10-time sit-to-stand was decreased significantly. This may be related to increase of leg and abdominal muscular strength. The exercise intervention program increased salivary 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activities significantly. These results suggested that 11β-HDS2 became the index for the increase of muscular strength to prevent LS.展开更多
Intrduction: Edema, Hypertension and Hypokalemia occur with inhibition of 11 B-Hydroxysteroid Dehydrogenase Type 2 (11B-HSD2) by chronic Licorice ingestion. However, a similar presentation following a chronic use of a...Intrduction: Edema, Hypertension and Hypokalemia occur with inhibition of 11 B-Hydroxysteroid Dehydrogenase Type 2 (11B-HSD2) by chronic Licorice ingestion. However, a similar presentation following a chronic use of another commonly used sweetener “Stevia” is not reported. Objective: To document a first case report of a subject presenting with Edema, Prehypertension and Hypokalemia induced by 11B-HSD2 inhibition induced by chronic ingestion of sweetener stevia. Case Report: 32 year old Caucasian woman presented with generalized edema (feet, hands and face) of over 6 months. She was noted to also manifest Prehypertension (138/88 mmHg) and Hypokalemia (3.4 mM/l). Laboratory tests revealed decline in serum aldosterone and plasma renin activity, an increase in plasma cortisol/cortisone ratio. On persistent interrogation, patient admitted to daily consumption of sweetener stevia for over 9 months. All the presenting manifestations resolved with normalization of the laboratory tests on withdrawal of stevia. Conclusion: This case report indicates that chronic ingestion of sweetener stevia may induce edema, hypertension and hypokalemia via reduced conversion of cortisol into cortisone by inhibition of 11 B-Hydroxysteroid Dehydrogenase Type 2.展开更多
11β-hydroxysteroid dehydrogenase (11β-HSD) in Leydig cells regulates sterodogenesis by controlling intra cellular glucocorticoid (corticosterone, B, in rat) concentration.Prior to the 26th postnatal day, 11β-HSD is...11β-hydroxysteroid dehydrogenase (11β-HSD) in Leydig cells regulates sterodogenesis by controlling intra cellular glucocorticoid (corticosterone, B, in rat) concentration.Prior to the 26th postnatal day, 11β-HSD is absent from rat immature Leydig cells. Asthe Leydig cells are matured, the enzyme is gradually produced. The highest levels of11β-HSD activity are present in adult rat Leydig cells. 11β-HSD controls the intracellular glucocorticoid concentration in Leydig cells and the glucocorticoids at the physiologicallevels also regulate levels of 11β-HSD activity in Leydig cells. The expressions of 11βHSD mRNA in Leydig cells from three different age groups of rats and adrenalectomizedrats (ADX), with and without B replacement were Observed in this study. The steady statelevels of 11β-HSD mRNA could not be detected in Leydig cells from immature rats aged21 days, but this could be detected in those aged 45 days. The highest levels of expressionOf 11β-HSD mRNA were found in adult Leydig cells. The mRNA expression of 11β-HSD was declined in Leydig cells after adrenalectomy, and this decline was prevented byB replacement (the levels were restored to control). The results indicated that 11β-HSDmRNA leVels expressed in three different age groups of rats are parallel with those ofantigen by immunohistochemical analysis and with those of enzyme activity by biochemicalmeasurement in previous studies. Similarly, the effect of B at physiological and endogenous levels on the expressions Of 11β-HSD mRNA corresponded to that on enzyme activity.展开更多
Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic C...Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic Chinese is unknown.The aim of this study was to investigate the potential associations in Chinese patients.Methods:In total,427 Han Chinese with biopsy-confirmed MAFLD were enrolled.Two single nucleotide polymorphisms in HSD17B13 were genotyped:rs72613567 and rs6531975.Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.Results:In our cohort,the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis[odds ratio(OR):2.93(1.20–7.17),p=0.019 for the additive model;OR:3.32(1.39–7.91),p=0.007 for the recessive model],representing an inverse association as compared to the results from European cohorts.In contrast,we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant[OR:0.48(0.24–0.98),p=0.043 for the additive model;OR:0.62(0.40–0.94),p=0.025 for the dominant model].HSD17B13 variants were only associated with fibrosis but no other histological features.Furthermore,HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.Conclusions:HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans.These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.展开更多
Estradiol (E2) is the major molecular form of estrogens. Its biological effects are determined by estrogen receptors and intracellular E2 concentration in target cells. Regulation of intracellular E2 concentration inv...Estradiol (E2) is the major molecular form of estrogens. Its biological effects are determined by estrogen receptors and intracellular E2 concentration in target cells. Regulation of intracellular E2 concentration involves the action of 17p-hydroxysteroid dehydrogenase (17HSD) type 2, the enzyme inactivating E2 to estrone. It has been demon-strated that 17HSD type 2 is expressed in normal endo-metrial epithelia and emdometrial carcinoma cells (RL 95-2). However, the regulatory mechanism of 17HSD type 2 expression in emdometrial cancer cells remains unknown. In the present study, the effects of transforming growth factor-β1 (TGF-β1) and epidermal growth factor (EGF) on 17HSD type 2 expression in RL 95-2 cells have been investigated using enzyme activity assay and Northern blot analysis. After stimulation with TGF-P1 or EGF, the in vivo oxidative 17HSD activity in RL 95-2 cells was significantly decreased. It appeared that the inhibitory effect of TGF-β1 and EGF onthe enzyme activity of 17HSD type 2展开更多
文摘The objective of the present study was to investigate the effects of genistein and equol on 3β-hydroxysteroid de- hydrogenase （3β-HSD） and 17β-hydroxysteroid dehydrogenase 3 （17β-HSD3） in human and rat testis microsomes. These enzymes （3β-HSD and 17β-HSD3）, along with two others （cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17α-hydroxylase/17-20 lyase）, catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3β-HSD activity （0.2 μmol L^-1 pregnenolone） with half-maximal inhibition or a half-maximal inhibitory concentration （IC50） of 87 ± 15 （human） and 636 ± 155 nmol L^-1 （rat）. Genistein＇s mode of action on 3β-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD＋. There was no difference in genistein＇s potency of 3β-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3β-HSD, genistein had lesser effects on human and rat 17β-HSD3 （0.1 μmol L^-1 androstenedione）, with an IC50 〉 100μmol L^-1. On the other hand, equol only inhibited human 3β-HSD by 42%, and had no effect on 3β-HSD and 17β-HSD3 in rat tissues. These observations imply that the ability of soy isoflavones to regulate androgen biosynthesis in Leydig cells is due in part to action on Leydig cell 3β- HSD activity. Given the increasing intake of soy-based food products and their potential effect on blood androgen levels, these findings are greatly relevant to public health.
文摘11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and localization of 11β-HSD in rat testis during postnatal development, and the regulation of these genes by luteinizing hormone （LH） and androgens, mRNA and protein levels were analyzed by quantitative real-time-polymerase chain reaction and western blotting, respectively, in testes collected from rats at postnatal day （PND） 7, 14, 21, 35, and 90, and from rats treated with LH, 7α.methyl-19-nortestosterone （MENT） and testosterone at PND 21 and PND 90. Immunohistochemical staining was used to identify the localization of the 11β-HSD in rat testis at PND 7, 14, and 90. We found that 11β-HSD1 expression was restricted to the interstitial areas, and that its levels increased during rat testis development. In contrast, whereas 11β-HSD2 was expressed in both the interstitial areas and seminiferous tubules at PND 7, it was present only in the interstitial areas at PND 90, and its levels declined during testicular development. Moreover, 11β-HSD1 mRNA was induced by LH in both the PND 21 and 90 testes and by MENT at PND 21, whereas 11β-HSD2 mRNA was induced by testosterone and MENT in the PND 21 testis and by LH in the PND 90 testis. In conclusion, our study indicates that the 11β-HSD1 and 11β-HSD2 genes have distinct patterns of spatiotemporal expression and hormonal regulation during postnatal development of the rat testis.
基金financially supported by the National Natural Science Foundation of China(General Program),No.31271494Excellent Talent Support Program of Liaoning Province,No.LJQ2011004
文摘3β-Hydroxysteroid-△24 reductase （DHCR24） is a multifunctional enzyme that localizes to the endoplasmic reticulum and has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuroprotection against apoptosis caused by amyloid β deposition. The present study aimed to construct two recombinant adenoviruses driving DHCR24 expression specifically in neurons. Two SYN1 promoter DNA fragments were obtained from human （h） and rat （r）. Recombinant Ad-r（h）SYN1-DHCR24 was transfected into AD-293, N2A （mouse neuroblastoma）, and MIN6 （mouse pancreatic carcinoma） cells. Western blot analysis showed DHCR24 was specially expressed in 293 and N2A cells, but no specific band was found in MIN6 cells. This demonstrates that the recombinant adenoviruses successfully express DHCR24, and no expression is observed in non-neuronal cells. TUNEL assay results showed apoptosis was inhibited in adenovirus-transfected neurons. Detecting reactive oxygen species by immunoflu- orescence, we found that adenovirus transfection inhibits apoptosis through scavenging excess reactive oxygen species. Our findings show that the recombinant DHCR24 adenoviruses induce neuron-specific DHCR24 expression, and thereby lay the foundation for further studies on DHCR24 gene therapy for Alzheimer＇s disease.
文摘It has been proposed that 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which activates glucocorticoids, plays a role in chronic inflammatory diseases including metabolic diseases, rheumatoid arthritis, and ulcerative colitis. We have recently reported that the expression of 11β-HSD1 is increased in the gingiva of patients with chronic periodontitis and in that of rats with ligature-induced periodontitis. In this study, to further demonstrate the involvement of 11β-HSD1 in chronic periodontitis, the expression of 11β-HSD1 was investigated in another rat model of experimental periodontitis induced by intragingival injection of lipopolysaccharide from Porphyromonas gingivalis (LPS-PG). Alveolar bone loss was observed two weeks after intragingival injection of LPS-PG. The level of 11β-HSD1 mRNA assessed by real-time reverse transcriptase-polymerase chain reaction was significantly elevated in LPS-PG-induced periodontitis compared with controls. The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids, was not significantly different between control and LPS-PG-induced periodontitis. The expression of 11β-HSD1 was significantly correlated with that of TNF in LPS-PG-induced periodontitis. The increased expression of 11β-HSD1 protein in LPS-PG-induced periodontitis was confirmed by immunohistochemistry using anti-11β-HSD1 antibody. These results further suggest a role for 11β-HSD1 in the pathogenesis of chronic periodontitis.
文摘Fourteen compounds of azastene and epostane derivatives (from YG101 to YG114) have been studied. Results showed that only YG102 and YG103 wore found to be positive in interceptivo activities, although they were less potent than their parent compound──azastene. Levels ofprogesterone in plasma were decreased significantly after administrstion or YG102, 103 and 106. Only YG107 possessed an interceptive activity approximately as potent as that of its paront compound──epostane. Epostane is a mixture of its enol and keto forms and the percentage of both forms defends on various condions. Since YG107 exists only in one form, we believe this derivative of epostane might be useful in the future work.
基金Supported by the National Natural Science Foundation of China(No.39970285),Shanghai Science and Technology Development Project(No.99JC14036)
文摘Objective: To study the effect of glucocorticoid on the promoter of the pre-receptor glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene. Methods: The 1. 2 kb length sequence upstream to the transcription start site of the 11β-HSD1 gene was amplified with polymerase chain reaction (PCR) and then was cloned into pBLCAT6 plasmid carrying chloramphenicol acetyltransferase ( CAT) reporter gene. The plasmid pBLCAT6 carrying the promoter and reporter gene was used to transfect HeLa cells to study the regulation of 11β-HSD1 gene expression by glucocorticoids in terms of reporter gene expression. Results: PCR showed that there was a complete alignment of the amplified sequence with the sequence 1. 2 kb upstream to the transcription start site of 11β-HSD1 gene. When cloned into pBLCAT6 plasmid carrying the reporter gene, this part of the promoter is functional in terms of regulation of reporter gene expression upon transfection into HeLa cells. The synthetic glucocorticoid-dexamethasone induced the reporter gene expression in the system described above, which was blocked by glucocorticoid receptor antagonist RU486. Conclusion: Glucocorticoids can modulate the expression of 11β-HSD1 through a mechanism involving activation of GR and interaction of the promoter of 11β-HSD1 gene.
文摘The Japanese Orthopedic Association proposed a concept called locomotive syndrome (LS) to identify middle-aged and older adults at high risk of requiring health care services because of problems with locomotion-associated lower muscle mass. To prevent LS, it is important to increase muscle mass and muscle strength in middle-age by continuous resistance training. A total of 38 men and women were assessed at baseline and 6 months. Body composition, physical strength and salivary cortisol and cortisone were analyzed. The exercise intervention program was performed by individual muscle endurance level. Body weight, muscle weight and basal metabolism were increased after exercise intervention. The 30-second sit-up test and 3-minute walking were increased, and the 10-time sit-to-stand was decreased significantly. This may be related to increase of leg and abdominal muscular strength. The exercise intervention program increased salivary 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activities significantly. These results suggested that 11β-HDS2 became the index for the increase of muscular strength to prevent LS.
文摘Intrduction: Edema, Hypertension and Hypokalemia occur with inhibition of 11 B-Hydroxysteroid Dehydrogenase Type 2 (11B-HSD2) by chronic Licorice ingestion. However, a similar presentation following a chronic use of another commonly used sweetener “Stevia” is not reported. Objective: To document a first case report of a subject presenting with Edema, Prehypertension and Hypokalemia induced by 11B-HSD2 inhibition induced by chronic ingestion of sweetener stevia. Case Report: 32 year old Caucasian woman presented with generalized edema (feet, hands and face) of over 6 months. She was noted to also manifest Prehypertension (138/88 mmHg) and Hypokalemia (3.4 mM/l). Laboratory tests revealed decline in serum aldosterone and plasma renin activity, an increase in plasma cortisol/cortisone ratio. On persistent interrogation, patient admitted to daily consumption of sweetener stevia for over 9 months. All the presenting manifestations resolved with normalization of the laboratory tests on withdrawal of stevia. Conclusion: This case report indicates that chronic ingestion of sweetener stevia may induce edema, hypertension and hypokalemia via reduced conversion of cortisol into cortisone by inhibition of 11 B-Hydroxysteroid Dehydrogenase Type 2.
文摘11β-hydroxysteroid dehydrogenase (11β-HSD) in Leydig cells regulates sterodogenesis by controlling intra cellular glucocorticoid (corticosterone, B, in rat) concentration.Prior to the 26th postnatal day, 11β-HSD is absent from rat immature Leydig cells. Asthe Leydig cells are matured, the enzyme is gradually produced. The highest levels of11β-HSD activity are present in adult rat Leydig cells. 11β-HSD controls the intracellular glucocorticoid concentration in Leydig cells and the glucocorticoids at the physiologicallevels also regulate levels of 11β-HSD activity in Leydig cells. The expressions of 11βHSD mRNA in Leydig cells from three different age groups of rats and adrenalectomizedrats (ADX), with and without B replacement were Observed in this study. The steady statelevels of 11β-HSD mRNA could not be detected in Leydig cells from immature rats aged21 days, but this could be detected in those aged 45 days. The highest levels of expressionOf 11β-HSD mRNA were found in adult Leydig cells. The mRNA expression of 11β-HSD was declined in Leydig cells after adrenalectomy, and this decline was prevented byB replacement (the levels were restored to control). The results indicated that 11β-HSDmRNA leVels expressed in three different age groups of rats are parallel with those ofantigen by immunohistochemical analysis and with those of enzyme activity by biochemicalmeasurement in previous studies. Similarly, the effect of B at physiological and endogenous levels on the expressions Of 11β-HSD mRNA corresponded to that on enzyme activity.
基金This work was supported by grants from the National Natural Science Foundation of China(82070588)High Level Creative Talents from Department of Public Health in Zhejiang Province(S2032102600032)+3 种基金Project of New Century 551 Talent Nurturing in Wenzhou.GT was supported in part by grants from the University School of Medicine of Verona(Verona,Italy)CDB was supported in part by the Southampton NIHR Biomedical Research Centre(ISBRC-20004)UK.ME and JG were supported by the Robert W.Storr Bequest to the Sydney Medical Foundation,University of Sydney(Sydney,Australia)and the National Health and Medical Research Council of Australia(NHMRC)Program(APP1053206,APP1149976)Project(APP1107178 and APP1108422)grants.
文摘Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic Chinese is unknown.The aim of this study was to investigate the potential associations in Chinese patients.Methods:In total,427 Han Chinese with biopsy-confirmed MAFLD were enrolled.Two single nucleotide polymorphisms in HSD17B13 were genotyped:rs72613567 and rs6531975.Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.Results:In our cohort,the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis[odds ratio(OR):2.93(1.20–7.17),p=0.019 for the additive model;OR:3.32(1.39–7.91),p=0.007 for the recessive model],representing an inverse association as compared to the results from European cohorts.In contrast,we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant[OR:0.48(0.24–0.98),p=0.043 for the additive model;OR:0.62(0.40–0.94),p=0.025 for the dominant model].HSD17B13 variants were only associated with fibrosis but no other histological features.Furthermore,HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.Conclusions:HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans.These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39700052).
文摘Estradiol (E2) is the major molecular form of estrogens. Its biological effects are determined by estrogen receptors and intracellular E2 concentration in target cells. Regulation of intracellular E2 concentration involves the action of 17p-hydroxysteroid dehydrogenase (17HSD) type 2, the enzyme inactivating E2 to estrone. It has been demon-strated that 17HSD type 2 is expressed in normal endo-metrial epithelia and emdometrial carcinoma cells (RL 95-2). However, the regulatory mechanism of 17HSD type 2 expression in emdometrial cancer cells remains unknown. In the present study, the effects of transforming growth factor-β1 (TGF-β1) and epidermal growth factor (EGF) on 17HSD type 2 expression in RL 95-2 cells have been investigated using enzyme activity assay and Northern blot analysis. After stimulation with TGF-P1 or EGF, the in vivo oxidative 17HSD activity in RL 95-2 cells was significantly decreased. It appeared that the inhibitory effect of TGF-β1 and EGF onthe enzyme activity of 17HSD type 2
