The MT10 mutant plants had resistances to auxin.Under light and dark culture,the roots of MT10 seedlings had shown less lateral roots and short lateral roots.In soil,MT10 seedlings had shown not only no changed agrono...The MT10 mutant plants had resistances to auxin.Under light and dark culture,the roots of MT10 seedlings had shown less lateral roots and short lateral roots.In soil,MT10 seedlings had shown not only no changed agronomic characteristics but also no significant difference with WT.展开更多
In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain,especially in the cerebellum.Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin.Our ...OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain,especially in the cerebellum.Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin.Our previous studies have shown brain CYP2D can be regulated by exogenous and endogenous substances with tissue-specificity.The purpose of this study is to examine the effects of cerebral CYP2D on the mice behavior and the regulatory mechanism of brain CYP2D by growth hormone.METHODS Mice received the stereotaxic injection with CYP2D inhibitor quinine in deep cerebellar nuclei of cerebellum.The animals were tested with rotarod apparatus,balance beam,water maze,elevated plus maze and open field.The changes in CYP2D22,PPARαand PPARγ in brain regions and liver were assayed in male growth hormone receptor knockout mice,SH-SY5 Y cells and HepG2 cells.RESULTS The inhibition of cerebellum CYP2D significantly affected the spatial learning and exploring ability of mice.Compared with WT mice,CYP2D expression was lower in brain regions from GHR(-/-)male mice;however,hepatic CYP2D level was similar.Pulsatile GH decreased PPARα m RNA level,and increased m RNA levels of CYP2D6 and PPARα in SH-SY5 Y cells.In HepG2 cells,pulsatile GH resulted in decreases in PPARα and PPARγ m RNA levels,but not CYP2D6.PPARα inhibitor induced CYP2D6 m RNA and protein by 1.32-fold and 1.43-fold in SH-SY5 Y cells.PPARγ inhibitor decreased CYP2D6 m RNA and protein by 74.76% and 40.93%.PPARα agonist decreased the level of CYP2D22 m RNA in liver and cerebellum,while PPARγ agonist rosiglitazone resulted in diametrically increases.The luciferase assay showed that PPARγ actived the CYP2D6 gene promoter while PPARα inhibited its function.Pulsatile GH declined the binding of PPARα with CYP2D6 promoter by 40%,promoted the binding of PPARγ with CYP2D6 promoter by approximate60%.The levels of brain and liver PPARα expression in male GHR(-/-)mice is obviously higher than those in WT mice.The level of PPARγ in male GHR(-/-)mice was decreased in the frontal cortex and hippocampus,while remained stable in the cerebellum and striatum;meanwhile,PPARγ was increased in the liver.CONCLUSION Brain CYP2D may be involved in learning and memory functions of central system.Masculine GH secretion altered the PPARs expression and the binding of PPARs to CYP2D promoter,leading to the elevated brain CYP2D in a tissue-specific manner.Growth hormone may specifically alter the metabolic and synthetic of important endogenous substances in the central nervous system(such as serotonin) through the specific regulation of brain CYP2D expression.展开更多
Single nucleotide polymorphisms(SNPs) of the growth hormone(GH) gene were investigated in six pig breeds,consisting of four mini-pig breeds(Wuzhishan,Bama,Xiang and Tibet pig),and two others(Dahlan and Landrace pig).T...Single nucleotide polymorphisms(SNPs) of the growth hormone(GH) gene were investigated in six pig breeds,consisting of four mini-pig breeds(Wuzhishan,Bama,Xiang and Tibet pig),and two others(Dahlan and Landrace pig).Three pairs of primers for promoter regions of the GH gene were designed on the basis of the pig genomic sequence and SNPs were detected by the PCR-SSCP method.The results indicated three mutations in the 5’-flanking region.The analysis results showed that the frequencies of allele A and D in four mini-pig breeds were higher than that in other breeds at a locus within the 5’-flanking region(P【0.05).These results suggest that differences in body size may be associated with these SNPs of 5’-flanking region and amino acid mutation of the signal peptide of GH in these pig breeds.展开更多
The objective of the study was to investigate the effects of dietary energy levels and sources on the blood metabolites,hormone secretion and the composition of follicular fluid in gilts.Fifty-four gilts with initial ...The objective of the study was to investigate the effects of dietary energy levels and sources on the blood metabolites,hormone secretion and the composition of follicular fluid in gilts.Fifty-four gilts with initial body weight of(59±4.2) kg were randomly allotted to six treatments.Treatments were low, normal,and high energy feeding levels,which were 87.5%,100%and 112.5%of recommendatory energy requirements by NRC(1998),respectively,and dietary energy sources(starch or fat).Blood samples and follicular fluids were collected on D18 and D19 of the second estrous cycle.The results showed that plasma concentrations of triglycerides and total cholesterol were higher in the fat group than that in the starch group(P【0.05),but those of glucose were similar between the two energy sources(P】0.05);dietary energy level exerted no effect on blood metabolites concentration(P】0.05).Gilts fed the high energy diet had a higher area under curve of plasma insulin(Insulin AUC),insulin-like growth factor-Ⅰ(IGF-Ⅰ) and leptin than did gilts fed the lower energy diet(P【0.05),but there was no significant difference between fat versus starch(P】0.05).Luteinizing hormone(LH) pulses were higher in gilts fed high energy rather than that in low energy diets(P】0.05),plasma concentration of estradiol(E<sub>2</sub>) was higher in the fat group than that in the starch group(P【0.05).The number of large follicles(diameter≥4 mm) and concentrations of IGF-Ⅰand E<sub>2</sub> in follicular fluid were increasing significant as the level of energy increased(P【0.05),but the numbers of large follicles and follicular fluid composition were not affected by the source of dietary energy(P】0.05).The results indicate that gilts fed high energy diets had elevated plasma concentrations of metabolic hormones,IGF-Ⅰand LH secretion,and increased follicular fluid concentrations of IGF-Ⅰ,E<sub>2</sub> and numbers of large follicles;gilts fed the dietary fat had a higher plasma concentration of cholesterol and E<sub>2</sub>.展开更多
Specific primers for the MC1R gene of alpacas(GenBank EU1358800) were designed to amplify the cDNA sequence using RT-PCR to seek variation in the sequence and explore the relationship between the expression level of M...Specific primers for the MC1R gene of alpacas(GenBank EU1358800) were designed to amplify the cDNA sequence using RT-PCR to seek variation in the sequence and explore the relationship between the expression level of MC1R gene and alpaca coat color.The MC1R gene from white alpaca was cloned successfully and sequence analysis verified that the MC1R gene,encoding 317 amino acids,was 1081 bp in length.Compared with the existing sequence in GenBank,sequence identity was 99.9%and 7 mutations were found.Primers,designed from the sequence obtained,were used to assess the relative expression of MC1R in alpacas of different coat color using QRT-PCR and SPSS 13.0 software.Relative expression of MC1R in the skin of brown alpacas was 4.32 times higher than that in white alpacas after normalization with GAPDH(P【0.01),indicating that MC1R expression may be related to coat color of alpacas.展开更多
Background Plant hormones profoundly influence cotton growth,development,and responses to various stresses.Therefore,there is a pressing need for an efficient assay to quantify these hormones in cotton.In this groundb...Background Plant hormones profoundly influence cotton growth,development,and responses to various stresses.Therefore,there is a pressing need for an efficient assay to quantify these hormones in cotton.In this groundbreaking study,we have established QuEChERS-HPLC‒MS/MS method,for the simultaneous detection of multiple plant hormones in cotton leaves,allowing the analysis and quantification of five key plant hormones.Results Sample extraction and purification employed 0.1%acetic acid in methanol and C18 for optimal recovery of plant hormones.The method applied to cotton demonstrated excellent linearity across a concentration range of 0.05–1 mg・L−1,with linear regression coefficients exceeding 0.99.The limits of quantification(LOQs)were 20μg・kg−1 for GA3 and 5μg・kg−1 for the other four plant hormones.Recovery rates for the five plant hormones matrix spiked at levels of 5,10,100,and 1000μg・kg−1 were in the range of 79.07%to 98.97%,with intraday relative standard deviations(RSDs)ranging from 2.11%to 8.47%.The method was successfully employed to analyze and quantify the five analytes in cotton leaves treated with plant growth regulators.Conclusion The study demonstrates that the method is well-suited for the determination of five plant hormones in cotton.It exhibits excellent selectivity and sensitivity in detecting field samples,thus serving as a robust tool for indepth research into cotton physiology.展开更多
In order to interpret pathologic mechanism of free radicals and thyroid hormone metabolism in cattle iodine and selenium deficiency, 20 heads of yellow cattle were selected from NiuJia town, Wu Chang City, Heilongjian...In order to interpret pathologic mechanism of free radicals and thyroid hormone metabolism in cattle iodine and selenium deficiency, 20 heads of yellow cattle were selected from NiuJia town, Wu Chang City, Heilongjiang Province, China, and were randomly devided into 4 groups with 5 for each. ① supplemented with 0.7 mg·kg -1 iodine(potassium iodine), ② supplemented with 0.2 mg·kg -1 selenium (sodium selenite), ③ supplemented with 0.7 mg·kg -1 iodine(potassium Iodine) plus 0.2 mg·kg -1 selenium (sodium selenite) per day for 30 days, respectively. ④control group. The whole blood glutathione peroxidase (GSH-px) and catalase (CAT) activities, free radicals (FR) concentration, erythrocyte superoxide dismutase (SOD) activity and molonaldehyde (MDA) concentration, the serum triiodothyronine (T 3)、thyroxine (T 4) and thyrotropin (TSH) were determined on the day of supplementation day-0 and day-30, respectively. It was showed that average iodine concentration in drinking water and diet were 3.82 μg·L -1 and 0.285mg·kg -1 , respectively, Diet selenium was 0.0498mg·kg -1 , Serum protein bound iodine(PBI) was 7.02 μg·100 mL, Blood selenium was 0.14 mg·L -1 , the schoolchildren′s goiter was 21.8%. It indicated that iodine and selenium were deficient in the investigated area. Whole blood GSH-px and CAT activities and serum T 3 concentration were significantly higher (P< 0.01 ), FR concentration and serum TSH were significantly lower(P<0.01) in the first three groups than that of the control, T 4 content in the first group was higher(P<0.05), T 4 was also higher (P>0.05) in the second group. and lower in the third group. The SOD and MDA in erythrocyte were not changed during the experimental period, The results also showed that GSH-px and CAT activities were increased, and FR decreased oberviously in the third group more than the other two groups, In addition, Thyroid hormone metabolism was more coincided with the physiologic status in the third group. the iodine and the selenium played an important role in the pathologic process of free radical metabolic disorder. selenium not only had the function of antioxidation by derectly scavenging free radicals, but also affected through GSH-px and CAT activities. iodine deficiency results in the Goiter, selenium deficiency aggravated iodine deficiency, Iodine and the selenium were dependent and restrained each other in the course of free radicals and thyroid hormone metabolism with a synergistic state.展开更多
Safety issues in hormonal therapy have been discussed in recent years especially in the field of hormone replacement therapy(HRT).The most important study Women's Health Initiative(WHI)has been stopped in 2002 due...Safety issues in hormonal therapy have been discussed in recent years especially in the field of hormone replacement therapy(HRT).The most important study Women's Health Initiative(WHI)has been stopped in 2002 due to increased risk of venous thromboembolism,myocardial infarction,stroke and breast cancer.This overview will concentrate on these main risks.There are options of different HRT regimens to minimize these risks.Especially plausible is the use of minimal dosages of transdermal administration avoiding first liver passage which should reduce hepatic and cardiovascular risks,which,however,is not based on placebo-controlled studies.For breast cancer development,first fear of most women,further research on the two main mechanisms are most importantproliferation effects and conditions for potential genotoxic estrogen metabolites.To individualize hormonal therapy also preexisting risks have to be considered,and with early start,within a"window of opportunity",most patients will benefit from HRT if indicated.展开更多
文摘The MT10 mutant plants had resistances to auxin.Under light and dark culture,the roots of MT10 seedlings had shown less lateral roots and short lateral roots.In soil,MT10 seedlings had shown not only no changed agronomic characteristics but also no significant difference with WT.
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
基金supported by National Natural Science Foundation of China(81673503 and 30973582)
文摘OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain,especially in the cerebellum.Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin.Our previous studies have shown brain CYP2D can be regulated by exogenous and endogenous substances with tissue-specificity.The purpose of this study is to examine the effects of cerebral CYP2D on the mice behavior and the regulatory mechanism of brain CYP2D by growth hormone.METHODS Mice received the stereotaxic injection with CYP2D inhibitor quinine in deep cerebellar nuclei of cerebellum.The animals were tested with rotarod apparatus,balance beam,water maze,elevated plus maze and open field.The changes in CYP2D22,PPARαand PPARγ in brain regions and liver were assayed in male growth hormone receptor knockout mice,SH-SY5 Y cells and HepG2 cells.RESULTS The inhibition of cerebellum CYP2D significantly affected the spatial learning and exploring ability of mice.Compared with WT mice,CYP2D expression was lower in brain regions from GHR(-/-)male mice;however,hepatic CYP2D level was similar.Pulsatile GH decreased PPARα m RNA level,and increased m RNA levels of CYP2D6 and PPARα in SH-SY5 Y cells.In HepG2 cells,pulsatile GH resulted in decreases in PPARα and PPARγ m RNA levels,but not CYP2D6.PPARα inhibitor induced CYP2D6 m RNA and protein by 1.32-fold and 1.43-fold in SH-SY5 Y cells.PPARγ inhibitor decreased CYP2D6 m RNA and protein by 74.76% and 40.93%.PPARα agonist decreased the level of CYP2D22 m RNA in liver and cerebellum,while PPARγ agonist rosiglitazone resulted in diametrically increases.The luciferase assay showed that PPARγ actived the CYP2D6 gene promoter while PPARα inhibited its function.Pulsatile GH declined the binding of PPARα with CYP2D6 promoter by 40%,promoted the binding of PPARγ with CYP2D6 promoter by approximate60%.The levels of brain and liver PPARα expression in male GHR(-/-)mice is obviously higher than those in WT mice.The level of PPARγ in male GHR(-/-)mice was decreased in the frontal cortex and hippocampus,while remained stable in the cerebellum and striatum;meanwhile,PPARγ was increased in the liver.CONCLUSION Brain CYP2D may be involved in learning and memory functions of central system.Masculine GH secretion altered the PPARs expression and the binding of PPARs to CYP2D promoter,leading to the elevated brain CYP2D in a tissue-specific manner.Growth hormone may specifically alter the metabolic and synthetic of important endogenous substances in the central nervous system(such as serotonin) through the specific regulation of brain CYP2D expression.
基金supported by National Natural Special Scientific and Techndogical Resources Sharing Platform (No.2005DKA21101)the 11th Five-year Plan of National Science and Technology Support(No.2006BAD73B08)the 15th Key Project"Chinese Experimental Miniature Pig Resources Development and Research Applications"Ministry of Science and Technology(No.2004BA717B- 01)
文摘Single nucleotide polymorphisms(SNPs) of the growth hormone(GH) gene were investigated in six pig breeds,consisting of four mini-pig breeds(Wuzhishan,Bama,Xiang and Tibet pig),and two others(Dahlan and Landrace pig).Three pairs of primers for promoter regions of the GH gene were designed on the basis of the pig genomic sequence and SNPs were detected by the PCR-SSCP method.The results indicated three mutations in the 5’-flanking region.The analysis results showed that the frequencies of allele A and D in four mini-pig breeds were higher than that in other breeds at a locus within the 5’-flanking region(P【0.05).These results suggest that differences in body size may be associated with these SNPs of 5’-flanking region and amino acid mutation of the signal peptide of GH in these pig breeds.
基金supported by Program for Changjiang Scholars and Innovative Research Team in University (IRT0555)National Natural Science Foundation (30471257) of China
文摘The objective of the study was to investigate the effects of dietary energy levels and sources on the blood metabolites,hormone secretion and the composition of follicular fluid in gilts.Fifty-four gilts with initial body weight of(59±4.2) kg were randomly allotted to six treatments.Treatments were low, normal,and high energy feeding levels,which were 87.5%,100%and 112.5%of recommendatory energy requirements by NRC(1998),respectively,and dietary energy sources(starch or fat).Blood samples and follicular fluids were collected on D18 and D19 of the second estrous cycle.The results showed that plasma concentrations of triglycerides and total cholesterol were higher in the fat group than that in the starch group(P【0.05),but those of glucose were similar between the two energy sources(P】0.05);dietary energy level exerted no effect on blood metabolites concentration(P】0.05).Gilts fed the high energy diet had a higher area under curve of plasma insulin(Insulin AUC),insulin-like growth factor-Ⅰ(IGF-Ⅰ) and leptin than did gilts fed the lower energy diet(P【0.05),but there was no significant difference between fat versus starch(P】0.05).Luteinizing hormone(LH) pulses were higher in gilts fed high energy rather than that in low energy diets(P】0.05),plasma concentration of estradiol(E<sub>2</sub>) was higher in the fat group than that in the starch group(P【0.05).The number of large follicles(diameter≥4 mm) and concentrations of IGF-Ⅰand E<sub>2</sub> in follicular fluid were increasing significant as the level of energy increased(P【0.05),but the numbers of large follicles and follicular fluid composition were not affected by the source of dietary energy(P】0.05).The results indicate that gilts fed high energy diets had elevated plasma concentrations of metabolic hormones,IGF-Ⅰand LH secretion,and increased follicular fluid concentrations of IGF-Ⅰ,E<sub>2</sub> and numbers of large follicles;gilts fed the dietary fat had a higher plasma concentration of cholesterol and E<sub>2</sub>.
基金supported by the National Natural Science Foundation of China(No.30501070)Shanxi Natural Science Foundation(No.20041099)President Foundation of Agricultural University of Hebei (BS2007023)
文摘Specific primers for the MC1R gene of alpacas(GenBank EU1358800) were designed to amplify the cDNA sequence using RT-PCR to seek variation in the sequence and explore the relationship between the expression level of MC1R gene and alpaca coat color.The MC1R gene from white alpaca was cloned successfully and sequence analysis verified that the MC1R gene,encoding 317 amino acids,was 1081 bp in length.Compared with the existing sequence in GenBank,sequence identity was 99.9%and 7 mutations were found.Primers,designed from the sequence obtained,were used to assess the relative expression of MC1R in alpacas of different coat color using QRT-PCR and SPSS 13.0 software.Relative expression of MC1R in the skin of brown alpacas was 4.32 times higher than that in white alpacas after normalization with GAPDH(P【0.01),indicating that MC1R expression may be related to coat color of alpacas.
基金National Key R&D Program of China(2022YFD1400300)Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural SciencesChina Agriculture Research System.
文摘Background Plant hormones profoundly influence cotton growth,development,and responses to various stresses.Therefore,there is a pressing need for an efficient assay to quantify these hormones in cotton.In this groundbreaking study,we have established QuEChERS-HPLC‒MS/MS method,for the simultaneous detection of multiple plant hormones in cotton leaves,allowing the analysis and quantification of five key plant hormones.Results Sample extraction and purification employed 0.1%acetic acid in methanol and C18 for optimal recovery of plant hormones.The method applied to cotton demonstrated excellent linearity across a concentration range of 0.05–1 mg・L−1,with linear regression coefficients exceeding 0.99.The limits of quantification(LOQs)were 20μg・kg−1 for GA3 and 5μg・kg−1 for the other four plant hormones.Recovery rates for the five plant hormones matrix spiked at levels of 5,10,100,and 1000μg・kg−1 were in the range of 79.07%to 98.97%,with intraday relative standard deviations(RSDs)ranging from 2.11%to 8.47%.The method was successfully employed to analyze and quantify the five analytes in cotton leaves treated with plant growth regulators.Conclusion The study demonstrates that the method is well-suited for the determination of five plant hormones in cotton.It exhibits excellent selectivity and sensitivity in detecting field samples,thus serving as a robust tool for indepth research into cotton physiology.
文摘In order to interpret pathologic mechanism of free radicals and thyroid hormone metabolism in cattle iodine and selenium deficiency, 20 heads of yellow cattle were selected from NiuJia town, Wu Chang City, Heilongjiang Province, China, and were randomly devided into 4 groups with 5 for each. ① supplemented with 0.7 mg·kg -1 iodine(potassium iodine), ② supplemented with 0.2 mg·kg -1 selenium (sodium selenite), ③ supplemented with 0.7 mg·kg -1 iodine(potassium Iodine) plus 0.2 mg·kg -1 selenium (sodium selenite) per day for 30 days, respectively. ④control group. The whole blood glutathione peroxidase (GSH-px) and catalase (CAT) activities, free radicals (FR) concentration, erythrocyte superoxide dismutase (SOD) activity and molonaldehyde (MDA) concentration, the serum triiodothyronine (T 3)、thyroxine (T 4) and thyrotropin (TSH) were determined on the day of supplementation day-0 and day-30, respectively. It was showed that average iodine concentration in drinking water and diet were 3.82 μg·L -1 and 0.285mg·kg -1 , respectively, Diet selenium was 0.0498mg·kg -1 , Serum protein bound iodine(PBI) was 7.02 μg·100 mL, Blood selenium was 0.14 mg·L -1 , the schoolchildren′s goiter was 21.8%. It indicated that iodine and selenium were deficient in the investigated area. Whole blood GSH-px and CAT activities and serum T 3 concentration were significantly higher (P< 0.01 ), FR concentration and serum TSH were significantly lower(P<0.01) in the first three groups than that of the control, T 4 content in the first group was higher(P<0.05), T 4 was also higher (P>0.05) in the second group. and lower in the third group. The SOD and MDA in erythrocyte were not changed during the experimental period, The results also showed that GSH-px and CAT activities were increased, and FR decreased oberviously in the third group more than the other two groups, In addition, Thyroid hormone metabolism was more coincided with the physiologic status in the third group. the iodine and the selenium played an important role in the pathologic process of free radical metabolic disorder. selenium not only had the function of antioxidation by derectly scavenging free radicals, but also affected through GSH-px and CAT activities. iodine deficiency results in the Goiter, selenium deficiency aggravated iodine deficiency, Iodine and the selenium were dependent and restrained each other in the course of free radicals and thyroid hormone metabolism with a synergistic state.
文摘Safety issues in hormonal therapy have been discussed in recent years especially in the field of hormone replacement therapy(HRT).The most important study Women's Health Initiative(WHI)has been stopped in 2002 due to increased risk of venous thromboembolism,myocardial infarction,stroke and breast cancer.This overview will concentrate on these main risks.There are options of different HRT regimens to minimize these risks.Especially plausible is the use of minimal dosages of transdermal administration avoiding first liver passage which should reduce hepatic and cardiovascular risks,which,however,is not based on placebo-controlled studies.For breast cancer development,first fear of most women,further research on the two main mechanisms are most importantproliferation effects and conditions for potential genotoxic estrogen metabolites.To individualize hormonal therapy also preexisting risks have to be considered,and with early start,within a"window of opportunity",most patients will benefit from HRT if indicated.