OBJECTIVE:To study the development mechanism of kidney-Yang deficiency through the establishment of support vector machine models of relevant hormones of the pituitary-target gland axes in rats with kidney-Yang defici...OBJECTIVE:To study the development mechanism of kidney-Yang deficiency through the establishment of support vector machine models of relevant hormones of the pituitary-target gland axes in rats with kidney-Yang deficiency syndrome.METHODS:The kidney-Yang deficiency rat model was created by intramuscular injection of hydrocortisone,and contents of the hormones of the pituita- ry-thyroid axis:thyroid stimulating hormone(TSH),3,3',5-triiodothyronine(T_3) and thyroxine(T_4);hormones of the pituitary-adrenal gland axis:adrenocorticotropic hormone(ACTH) and Cortisol(CORT);and hormones of the pituitary-gonadal axis:luteinizing hormone(LH),follicle-stimulating hormone(FSH),and testosterone(T),were determined in the early,middle,and advanced stages.Ten support vector regression(SVR) models of the hormones were established to analyze the mutual relationships among the hormones of the three axes.RESULTS:The feedback control action of the pituitary-adrenal axis began to lose efficacy from the middle stage of kidney-Kong deficiency.The contents all hormones of the three pituitary-target gland axes decreased in the advanced stage.Relative errors of the jackknife test of the SVR models all were less than 10%.CONCLUSION:Imbalances in mutual regulation among the hormones of the pituitary-target gland axes,especially loss of effectiveness of the pituitary-adrenal axis,is one pathogenesis of kidney-Yang deficiency.The SVR model can accurately reflect the complicated non-linear relationships among pituitary-target gland axes in rats with of kidney-Yang deficiency.展开更多
Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadot...Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone （GnRH） action. Because reduced or normal luteinizing hormone （LH）/follicle-stimulating hormone （FSH） levels may be observed in the affected patients, the term idiopathic central hypogonadism （ICH） appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome （KS）. KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH （nlCH）, justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.展开更多
The European beaver (Castor fiber L.) is the largest free-living rode nt in Eurasia. The prese nt work aimed to determi ne sex- and seas on-related cha nges in leptin receptor (Ob-R) expression in the hypothalamic-pit...The European beaver (Castor fiber L.) is the largest free-living rode nt in Eurasia. The prese nt work aimed to determi ne sex- and seas on-related cha nges in leptin receptor (Ob-R) expression in the hypothalamic-pituitary-gonadal/adrenal axes and uterus of beavers during breeding-(April), postbreeding-(July), and pre-breeding-(November) periods. The expression of Ob-R gene and protein was found in all analyzed tissues. The expression of Ob-R mRNA remained constant in the hypothalamus of both sexes during the analyzed stages. Sex- and season-related changes were found in the pituitary gland;the greatest level was observed in July in both sexes. The same expression pattern was noted in the testis, whereas in the ovary a lack of seasonal changes was found. In uterine tissues, the greatest expression occurred in November. The impact of season was also demonstrated in the adrenal cortex. In females, a higher Ob-R transcript level was noted in April, while in males, an increased mRNA abundanee was noted in November than July. Our study suggests that in the beaver, leptin acting via the Ob-R can be an important endocrine factor engaged in the regulation of reproductive functions and stress response.展开更多
The aim of this study was to determine whether testicular volume is correlated with clinical and biochemical markers of hypothalamic–pituitary–testicular(HPT)axis function.This was a cross-sectional substudy of a la...The aim of this study was to determine whether testicular volume is correlated with clinical and biochemical markers of hypothalamic–pituitary–testicular(HPT)axis function.This was a cross-sectional substudy of a larger randomized controlled trial including obese men,body mass index(BMI)≥30 kg m−2,with a total testosterone level<12 nmol l−1.Testicular volume was measured by orchidometer,testosterone by liquid chromatography/tandem mass spectrometry,and body composition by dual-energy X-ray absorptiometry.Men completed the Aging Males'Symptoms(AMS)score,International Index of Erectile Function-5(IIEF-5),physical function,and handgrip dynamometer testing.Eighty-nine men participated with a median(interquartile range[IQR])age of 53.1(47.6,59.2)years,BMI of 37.0(34.6,40.5)kg m−2,and a total testosterone of 7.0(6.1,7.9)nmol l−1.Median testicular volume was 18(IQR:10,20)ml.Testicular volume was negatively correlated with BMI(τ=−0.1952,P=0.010)and total fat mass(τ=−0.2115,P=0.005)independent of age and testosterone.When BMI,testosterone,sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were present in a multivariable model,only BMI(-0.38 ml change in testicular volume per 1 kg m-2BMI;95%CI:−0.74,−0.02;P=0.04)and LH(-0.92 ml change in testicular volume per 1 IU l-1 LH;95%CI:−1.75,−0.095;P=0.03)remained independent significant predictors of testicular volume.Testicular volume was positively correlated with IIEF-5(τ=0.2092,P=0.021),but not related to handgrip strength,physical function tests,or AMS.In obese men,testicular volume is inversely and independently associated with measures of adiposity,but not with most clinical or biochemical markers of HPT axis action.From a clinical perspective,this suggests that obesity might compromise the reliability of reduced testicular volume as a sign of androgen deficiency in men.展开更多
Endocrine disrupting chemicals （EDCs） are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes （DMRT, VTG, GnRHR, FSHR, CYP1...Endocrine disrupting chemicals （EDCs） are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes （DMRT, VTG, GnRHR, FSHR, CYP17A, CYP19A, and CYP19B） involved in sex steroid synthesis and action as well as sexual development in adult male and female Cynoglossus semilaevis, after exposure to different concentrations ofBisphenol A （BPA） and 17[3-estradiol （E2）. Both BPA （1, 10, 50, 125, and 250 mg/kg） and E2 （0.5, 5, and 10 mg/kg） induced changes in target gene expression, although the estrogenic effects orE2 as a model estrogen were stronger. Among the 7 genes, VTG, CYP17A and CYP19 responded strongly to BPA or E2 exposure and can thus serve as reference biomarkers for estrogenic EDCs exposure in marine teleosts. These data will provide a window to establish a hypothalamic-pituitary-gonadal model in C. semilaevis to better understand the effect pathways of EDCs.展开更多
基金Supported by National Natural Science Foundation for Young Scholars of China(Study on the Mechanism of Kidney-Yang Deficiency Regulation with Yougui Pill Base on Support Vector Regression Machine,No.81403153)National Natural Science Foundation of China(General Program,Study on the Mechanisms of the Premature Ovarian Failure Regulation by Herbs Couples of Cuscuta Chinessis-Radix Bupleuri in Dingjing Decoction based on RBF Artificial Neural Networks,No.81073073) and National Natural Science Foundation of China(General Program,Study on the law of compatibility of Categorized Formula for Tonifying Kidney Yang based on Rough Set,No.30973977)
文摘OBJECTIVE:To study the development mechanism of kidney-Yang deficiency through the establishment of support vector machine models of relevant hormones of the pituitary-target gland axes in rats with kidney-Yang deficiency syndrome.METHODS:The kidney-Yang deficiency rat model was created by intramuscular injection of hydrocortisone,and contents of the hormones of the pituita- ry-thyroid axis:thyroid stimulating hormone(TSH),3,3',5-triiodothyronine(T_3) and thyroxine(T_4);hormones of the pituitary-adrenal gland axis:adrenocorticotropic hormone(ACTH) and Cortisol(CORT);and hormones of the pituitary-gonadal axis:luteinizing hormone(LH),follicle-stimulating hormone(FSH),and testosterone(T),were determined in the early,middle,and advanced stages.Ten support vector regression(SVR) models of the hormones were established to analyze the mutual relationships among the hormones of the three axes.RESULTS:The feedback control action of the pituitary-adrenal axis began to lose efficacy from the middle stage of kidney-Kong deficiency.The contents all hormones of the three pituitary-target gland axes decreased in the advanced stage.Relative errors of the jackknife test of the SVR models all were less than 10%.CONCLUSION:Imbalances in mutual regulation among the hormones of the pituitary-target gland axes,especially loss of effectiveness of the pituitary-adrenal axis,is one pathogenesis of kidney-Yang deficiency.The SVR model can accurately reflect the complicated non-linear relationships among pituitary-target gland axes in rats with of kidney-Yang deficiency.
文摘Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone （GnRH） action. Because reduced or normal luteinizing hormone （LH）/follicle-stimulating hormone （FSH） levels may be observed in the affected patients, the term idiopathic central hypogonadism （ICH） appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome （KS）. KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH （nlCH）, justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.
文摘The European beaver (Castor fiber L.) is the largest free-living rode nt in Eurasia. The prese nt work aimed to determi ne sex- and seas on-related cha nges in leptin receptor (Ob-R) expression in the hypothalamic-pituitary-gonadal/adrenal axes and uterus of beavers during breeding-(April), postbreeding-(July), and pre-breeding-(November) periods. The expression of Ob-R gene and protein was found in all analyzed tissues. The expression of Ob-R mRNA remained constant in the hypothalamus of both sexes during the analyzed stages. Sex- and season-related changes were found in the pituitary gland;the greatest level was observed in July in both sexes. The same expression pattern was noted in the testis, whereas in the ovary a lack of seasonal changes was found. In uterine tissues, the greatest expression occurred in November. The impact of season was also demonstrated in the adrenal cortex. In females, a higher Ob-R transcript level was noted in April, while in males, an increased mRNA abundanee was noted in November than July. Our study suggests that in the beaver, leptin acting via the Ob-R can be an important endocrine factor engaged in the regulation of reproductive functions and stress response.
基金MNTF was supported an ESA-RACP research establishment fellowship and MG by a career Developm ent Fellow(1024139)from the NHM RCBayer Pharm a AG(Berlin,G erm any)provided testosterone,placebo and financial support to conduct investigation during the RCT phase.
文摘The aim of this study was to determine whether testicular volume is correlated with clinical and biochemical markers of hypothalamic–pituitary–testicular(HPT)axis function.This was a cross-sectional substudy of a larger randomized controlled trial including obese men,body mass index(BMI)≥30 kg m−2,with a total testosterone level<12 nmol l−1.Testicular volume was measured by orchidometer,testosterone by liquid chromatography/tandem mass spectrometry,and body composition by dual-energy X-ray absorptiometry.Men completed the Aging Males'Symptoms(AMS)score,International Index of Erectile Function-5(IIEF-5),physical function,and handgrip dynamometer testing.Eighty-nine men participated with a median(interquartile range[IQR])age of 53.1(47.6,59.2)years,BMI of 37.0(34.6,40.5)kg m−2,and a total testosterone of 7.0(6.1,7.9)nmol l−1.Median testicular volume was 18(IQR:10,20)ml.Testicular volume was negatively correlated with BMI(τ=−0.1952,P=0.010)and total fat mass(τ=−0.2115,P=0.005)independent of age and testosterone.When BMI,testosterone,sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were present in a multivariable model,only BMI(-0.38 ml change in testicular volume per 1 kg m-2BMI;95%CI:−0.74,−0.02;P=0.04)and LH(-0.92 ml change in testicular volume per 1 IU l-1 LH;95%CI:−1.75,−0.095;P=0.03)remained independent significant predictors of testicular volume.Testicular volume was positively correlated with IIEF-5(τ=0.2092,P=0.021),but not related to handgrip strength,physical function tests,or AMS.In obese men,testicular volume is inversely and independently associated with measures of adiposity,but not with most clinical or biochemical markers of HPT axis action.From a clinical perspective,this suggests that obesity might compromise the reliability of reduced testicular volume as a sign of androgen deficiency in men.
基金Supported by the special funds for the Basic R&D Program in the Central Non-profit Research Institutes(No.2060302)
文摘Endocrine disrupting chemicals （EDCs） are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes （DMRT, VTG, GnRHR, FSHR, CYP17A, CYP19A, and CYP19B） involved in sex steroid synthesis and action as well as sexual development in adult male and female Cynoglossus semilaevis, after exposure to different concentrations ofBisphenol A （BPA） and 17[3-estradiol （E2）. Both BPA （1, 10, 50, 125, and 250 mg/kg） and E2 （0.5, 5, and 10 mg/kg） induced changes in target gene expression, although the estrogenic effects orE2 as a model estrogen were stronger. Among the 7 genes, VTG, CYP17A and CYP19 responded strongly to BPA or E2 exposure and can thus serve as reference biomarkers for estrogenic EDCs exposure in marine teleosts. These data will provide a window to establish a hypothalamic-pituitary-gonadal model in C. semilaevis to better understand the effect pathways of EDCs.
